Nature Communications
·
2025
·Vol. 16
·期 1
·1-13
·
IF 15.7
Li Fei,Yuan Zhenbo,Gao Yue,Deng Zhiwei,Zhang Yan,Luo Zhengshan,Rao Yijian
The application and drug development of plant-derived natural products are often limited by their low abundance in medicinal plants and the lack of structural complexity and diversity. Herein, we design a concise enzyme cascade to efficiently produce natural and unnatural protoberberine alkaloids from cost-effective, readily available substrates. Through enzyme discovery and engineering, along with systematic optimization of the berberine bridge enzyme to address remaining manufacturing challenges in protoberberine alkaloid biosynthesis, the high production of drug Rotundine is achieved at an impressive gram-scale titer, demonstrating its industrial potential. More importantly, this cascade also enables the efficient biosynthesis of various unnatural halogenated protoberberine alkaloids. Thus, this work not only unlocks the potential of enzyme cascades in overcoming longstanding challenges in the efficient biosynthesis of plant-derived alkaloids, but also opens avenues to introduce structural complexity and diversity into alkaloids through synthetic biology, offering significant potential for drug development.
研究领域:
生物化学
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合成生物学
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药物开发
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DOI
PubMed
高影响因子
FITOTERAPIA
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2025
·
IF 2.6
Li-Li Ye,Meng-Yue Yang,Xiang-Hai Cai
Eight new gelsedine-type oxindole alkaloids and ten known analogues were isolated from the stems and leaves of Gelsemium elegans . Gelseansdine A ( 1 ) was an N 4 -deficient Gelsemium alkaloid, while gelseansdines E–H ( 12 , 14 , 16 – 17 ) represented a class of alkaloids polymerized with iridoid. Their structures were elucidated based on UV, HRESIMS, NMR spectroscopy, and electronic circular dichroism (ECD) data analyses. Additionally, the isolated compounds were screened for their inhibitory activity on macrophage M2 polarization.
研究领域:
植物化学
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药物化学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2018
·Vol. 16
·期 48
·9430-9439
·
IF 3.423
Si-Fan Liu,Bin Lin,Yu-Fei Xi,Le Zhou,Li-Li Lou,Xiao-Xiao Huang,Xiao-Bo Wang,Shao-Jiang Song
Four pairs of new spiropyrrolizidine oxindole enantiomers (1a/1b–4a/4b) were isolated from the leaves of Isatis indigotica Fortune. Their structures and absolute configurations were elucidated by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD) and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Notably, all the isolated spiropyrrolizidine oxindoles are reported as natural products for the first time. The biosynthetic pathway of these unique structures was proposed to be formed by cycloaddition reaction. In addition, all the compounds were evaluated for their inhibitory effects on β-amyloid aggregation by ThT assay, and the optically pure compounds 1a/1b and 2a/2b exhibited better Aβ1–42 aggregation inhibition potency (85.8% and 73.6%, 71.5% and 75.8%, respectively) at a concentration of 20 μM, compared with the positive control curcumin (57.0%). The difference of the inhibitory pattern caused by chirality was also explained by molecular docking studies.
研究领域:
天然产物化学
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药理学
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量子化学计算
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
·
IF 3.69
Wei Zhang,Mengjiao Wang,Huijie Song,Chengfeng Gao,Dongmei Wang,Huiming Hua,Yingni Pan,Xiaoqiu Liu
Ethnopharmacological relevance Evodiae Fructus (EF), the traditional Chinese medicine , has been typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It is a mild toxicity herb-medicine listed in Sheng Nong's Herbal Classic . Recently, EF was reported to have toxicity or no toxicity in some investigations. Toxicity and approaches to reducing toxicity of EF are of great interest. Limonin (LIM), a major triterpenoid component of EF, also had various pharmacological activities such as anti-inflammatory, anticancer, and antioxidant effects. However, little attention was paid to the role of LIM in EF-induced hepatotoxicity. Aim of study The study aimed to address the problem of controversial hepatotoxicity of EF, evaluate the role of CYP3A4 inducer/inhibitor in EF-induced hepatotoxicity and disclose the effect of LIM in EF-induced hepatotoxicity. Materials and methods The chemical compositions and hepatotoxicity of small flower EF (SEF), medium flower EF (MEF), big flower EF (BEF) and the “organ knock-out” samples (the shell and seed part of BEF) were investigated. Simultaneously, C57BL-6 mice were randomly divided into four groups, which were given orally administered BEF, BEF in combination with dexamethasone (DEX), BEF in combination with ketoconazole (KTC), and BEF in combination with LIM, respectively. Results In this study, more alkaloids and less LIM were detected in BEF compared with the compounds in SEF and MEF. Furthermore, we found that BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in SEF and MEF groups. In addition, no LIM was detected in the shell part of BEF and five alkaloids were not detected in the seed part of BEF. Correspondingly, the shell part of BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in the seed part of BEF group. It was also found that the BEF-induced hepatotoxicity was remarkably exacerbated when the mice were pretreated with DEX whereas the BEF-induced hepatotoxicity could be reversed by pretreatment with KTC or LIM. Conclusions Based on the results in this study, the misuse of BEF but not SEF and MEF could produce hepatotoxicity. The hepatotoxicity difference of different categories of EF might be associated with the relative contents of alkaloids and LIM. In addition, the results demonstrated that CYP3A4 inducer aggravated BEF-induced hepatotoxicity and LIM attenuated its hepatotoxicity.
研究领域:
民族药理学
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毒理学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Qian Wan,Jie Xu,Chengjing Zhu,Xingxing Liu,Yijun Tu,Jiachuan Lei,Jianqing Yu
Piper longum L. is widely cultivated for food, medicine, and other purposes in tropical and subtropical regions. Sixteen compounds including nine new amide alkaloids were isolated from the roots of P. longum. The structures of these compounds were determined by spectroscopic data. All compounds showed better anti-inflammatory activities (IC50 = 1.90 ± 0.68–40.22 ± 0.45 μM) compared to indomethacin (IC50 = 52.88 ± 3.56 μM). Among the isolated compounds, five dimeric amide alkaloids exhibited synergistic effects with three chemotherapeutic drugs (paclitaxel, adriamycin, or vincristine) against cervical cancer cells. Moreover, these dimeric amide alkaloids also enhanced the efficacy of paclitaxel in paclitaxel-resistant cervical cancer cells. The combination treatment of one of these dimeric amide alkaloids and paclitaxel promoted cancer cell apoptosis, which is related to the Src/ERK/STAT3 signaling pathway.
研究领域:
药理学
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肿瘤学
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化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2017
·
IF 0
Min Liu,Yan Cao,Diya Lv,Wen Zhang,Zhenyu Zhu,Hai Zhang,Yifeng Chai
According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids, monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats were used for validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diester-diterpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids. Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.
研究领域:
中药学
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药理学
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DOI
PubMed
EUROPEAN FOOD RESEARCH AND TECHNOLOGY
·
2017
·Vol. 244
·期 5
·851-860
·
IF 1.664
Xu Dan,Liu Hong,Jin Cheng-yu,Cao Chun-mei,Li Wen-gang,Zeng Fan-kui,Zhao Yu-ci,Liu Gang
Hongmei is a new potato variety developed in recent year, which is suitable for raw eating as a kind of fruit. In this study, sensory evaluations, nutritional components, morphology characteristics of starch granules, phenolic compounds, sugars, glycoalkaloids, and amino acid composition of potato Hongmei were investigated. The results show that Hongmei be suitable for raw eating mainly based on three reasons: (1) possess a juicy characteristic and lower earthy smell, with a distinctive fruity flavor of fresh cucumber; (2) the average particle size of starch from Hongmei is 18.31 ± 7.71 μm, which is smaller than the commercial potato starch significant ( p < 0.01); (3) with a content of 653.64 ± 83.25 mg/100 g of fructose, which is similar to the sweet potato be suitable for raw eating. The results also show that Hongmei had high concentrations of crude protein, total ascorbic acid, but lower starch content. The total glycoalkaloids content in the flesh is only 5.52 mg/kg, which implied that it is safe for raw eating. However, due to the total glycoalkaloids in the Hongmei peel is 358.88 mg/kg, which is higher than the safe standard of 200 mg/kg, it is recommended to peel when eating raw.
研究领域:
食品科学
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植物学
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DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Zetong Cheng,Cheng Yao,Zhihao Chen,Kun Hu,Pinhuang Luo,Kewei Liu,Tian-Ao Zhang,Jiajun Hu,Min-Tian Gao
Strobilanthes cusia is a traditional Chinese medicinal herb containing indole alkaloids, key bioactive components responsible for its pharmacological effects. However, there has been limited research regarding S. cusia compositional impact on antimicrobial properties. This study centered around the hydrolysis and oxidative condensation reactions of indican, aiming to investigate the influence of its intermediate, indoxyl, on pathogenic bacteria growth and biofilm formation. A notable inhibitory effect of indoxyl on Staphylococcus aureus biofilm formation was found. High-performance liquid chromatography and transmission electron microscopy confirmed that indoxyl disrupted the membrane structure of biofilm cells, causing a disturbance in cellular redox balance. These findings suggest that the oxidative reaction of indoxyl within cells could be a prominent factor affecting cell viability. Simultaneously, a portion of indoxyl oxidized externally to form indigo, which did not affect intracellular activities but rather disrupted the biofilm structure. The concept of “compositional changes” enriches the understanding of antimicrobial properties of S. cusia , offering novel approaches for effectively inhibiting pathogenic microorganisms.
研究领域:
药用植物学
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微生物学
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药物化学
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产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2019
·
IF 3.926
Eryan Guo,Yunwei Hu,Tao Du,Huilin Zhu,Lei Chen,Wei Qu,Jie Zhang,Ning Xie,Wenyuan Liu,Feng Feng,Jian Xu
Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l -glutamate-stimulated PC12 and Aβ 25-35 -stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-β peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Aβ 1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six β-carboline alkaloids ( 1 – 6 ), seven canthin-6-one alkaloids ( 7 – 13 ), and five quassinoids ( 14 – 18 ). Among them, four β-carbolines ( 1 – 3 , and 6 ) and six canthin-6-ones ( 7 – 11 , and 13 ) exhibited potential neuroprotective activities in vitro . Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE).
研究领域:
神经科学
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药理学
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中医药
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分子生物学
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DOI
PubMed
高影响因子
CHROMATOGRAPHIA
·
2012
·Vol. 75
·期 9
·499-511
·
IF 1.195
Zhang Chunhua,Wu Huiqin,Huang Xiaolan,Zhu Zhixin,Luo Huitai,Huang Fang,Lin Xiaoshan
A sensitive and selective method for simultaneous determination of 29 toxic alkaloids in human blood and 31 in urine using high-performance liquid chromatography–electrospray ionization-tandem mass spectrometry was developed and validated. The samples were diluted with 0.1 mol L −1 HCl, and the target alkaloids were purified by solid phase extraction. The separation of 31 alkaloids was carried out on a C18 column using a gradient mobile phase with 10 mmol L −1 ammonium formate in water with 0.1% formic acid and methanol at the rate of 0.25 mL min −1 . The triple-quadrupole mass spectrometer equipped with an electrospray source in the positive mode was set up in the dynamic multiple reactions monitoring mode (dynamic MRM) to detect the ion transitions of 31 alkaloids. The calibration curves were linear over a range of 0.5–400, 1–400, or 4–400 μg L −1 for target alkaloids in human blood and urine, and the correlation coefficients ( r
2 ) was higher than 0.9943. The limit of determination and limit of quantification were 0.2–1 and 0.5–4 μg L −1 for blood and urine, respectively. The only exceptions were sanguinarine and chelerythrine in human blood. All the target alkaloids were stable under the test condition. In addition, the solvent effect and reconstituted solution were investigated. The method was validated and proved to be accurate and precise over the studied concentrations and suitable for poisoning diagnosis and forensic toxicology.
研究领域:
分析化学
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法医学
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毒理学
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产品关联
DOI
高影响因子
PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS
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2020
·Vol. 26
·期 7
·1425-1435
·
IF 2.005
Song Cheng,Jiao Chunyan,Jin Qing,Chen Cunwu,Cai Yongping,Lin Yi
Nitrogen-containing compounds especially alkaloids are important medicinal ingredients in caulis dendrobii plants. Using solid-phase extraction coupled with liquid chromatography tandem mass spectrometry and multivariate data analysis methods, metabolic profiling of the nitrogen-containing compounds was established to distinguish Dendrobium huoshanense and Dendrobium officinale . Hundreds of nitrogen-containing compounds from the two caulis dendrobii were purified by the MCX cartridges. Some compounds were identified by high-resolution tandem mass spectrometry technology. Together with multivariate data analysis methods, comparative analysis of the metabolic profiling from two caulis dendrobii was conducted. A total of 133 nitrogen-containing compounds were identified, including amino acids, pyrrolidines, tropanes, pyrimidines, purines, indoles, piperidines, guanidines, quinolines, isoquinolines and terpenoids. Metabolic profiling analysis showed that the composition and contents of these chemical components were significantly different between D. huoshanense and D. officinale . Moreover, some components were species-specific, distributed in the two caulis dendrobii, such as pilosine, ternatusine, etc. Because alkaloids are mainly derived from amino acids via multistep biochemical reactions, the correlation analysis suggested that amino acids were partially associated with several types of components and significantly correlated with certain alkaloids. Arginine was extremely correlated with guanidines. Pyrimidines, purines and niacin-nicotinamide metabolic intermediates were associated with three independent networks. The results further enriched the chemical components currently identified from caulis dendrobii and provided a technical reference for detecting nitrogen-containing compounds in other medicinal plants.
研究领域:
植物化学
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药用植物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 7
·1391-1403
·
IF 3.645
Ning Wang,Yue-Wu Xie,Meng-Yu Li,Fei-Fei Li,Li-Yuan Zhang,Yu-Lin You,Shu-Qi Wang
Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple-reaction-monitoring mode with an electrospray positive-ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single-dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.
研究领域:
药理学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
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