Natural Product Communications
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2018
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IF 0.809
Jianhua Zhu,Shuijie He,Pengfei Zhou,Jiachen Zi,Jincai Liang,Liyan Song,Rongmin Yu
Vallesiachotamine and isovallesiachotamine are pharmacologically active monoterpene indole alkaloids produced by Catharanthus roseus. However, the biosynthetic pathway for these two alkaloids has not been characterized. The results of our experiments demonstrated that catharanthine induced the biosynthesis of vallesiachotamine and isovallesiachotamine in C. roseus cambial meristematic cells (CMCs) in a time- and dosage-dependent manner. The highest yields of vallesiachotamine and isovallesiachotamine (i.e., 1.49 mg l−1 and 1.08 mg l−1, respectively) were observed in CMCs treated with 10 mg catharanthine l−1 for 12 h. The cells growth was inhibited by 20 mg catharanthine l−1 (i.e., 16.3% decrease in dry-cell weight). A quantitative reverse transcription polymerase chain reaction analysis revealed that catharanthine regulated the biosynthesis of vallesiachotamine and isovallesiachotamine by up-regulating the expression of specific genes, including STR (strictosidine synthase), SGD (strictosidine β-D-glucosidase) and ORCA3 (transcription factor octadecanoid-responsive Catharanthus AP2/ERF-domain 3). Finally, considering the up-regulated expression of STR and SGD was consistent with the accumulation of vallesiachotamine and isovallesiachotamine, a potential vallesiachotamine and isovallesiachotamine biosynthetic pathway was proposed.
研究领域:
植物学
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药理学
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植物生物技术
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分子生物学
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产品关联
DOI
高影响因子
PLANT CELL TISSUE AND ORGAN CULTURE
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2025
·Vol. 162
·期 3
·1-12
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IF 2.4
Li Haihua,Li Jiahe,Liu Ningjin,Li Huishan,Wang Jiarui,Zhang Rulan,Xue Jingyan,Kang Xiaotian,Guan Xinying,Lin Shiya,Zhang Ziyu,Kuang Jiaqi,Qian Chenlei,Zhou Pengfei
In Catharanthus roseus , the inherently low yield of bioactive alkaloids such as vindoline, catharanthine, ajmalicine, and vinblastine remains a major limitation to their broader therapeutic application, particularly in anticancer and antihypertensive treatments. To address this challenge, we developed a novel metabolic flux regulation strategy by combining the enzyme inhibitors lovastatin and naproxen with the abiotic elicitor copper(II)-chitosan (Cu-CS) complex. Compared to controls, treatment with 2 mg/L lovastatin significantly enhanced catharanthine, vindoline, ajmalicine, and vinblastine accumulation in C. roseus CMCs to 2.38, 0.63, 35.3, and 2.33 mg/L, respectively — increases of 48%, 121%, 71%, and 12%. Application of 8 mg/L naproxen further enhanced catharanthine, vindoline, and vinblastine levels to 3.78, 0.67, and 2.14 mg/L, representing increases of 151%, 135%, and 30%, respectively. The Cu-CS complex at 10 mg/L elevated catharanthine, vindoline, ajmalicine, and vinblastine to 2.13, 0.49, 32.11, and 2.46 mg/L, with corresponding increases of 49%, 63%, 55%, and 36%. Notably, the combined treatment of all three agents synergistically boosted catharanthine, vindoline, and vinblastine production to 5.94, 1.52, and 3.65 mg/L — representing 310%, 390%, and 98% increases over control levels. Quantitative RT-PCR analysis revealed that Cu-CS treatment upregulated the transcription of key genes and transcription factors involved in terpenoid indole alkaloid (TIA) biosynthesis. Overall, this integrated strategy effectively redirects metabolic flux toward enhanced TIA production in C. roseus CMCs, providing a practical and efficient approach for improving the yield of pharmaceutically important alkaloids in plant cell culture systems.
研究领域:
植物生物技术
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次生代谢
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医药生物技术
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分子生物学
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代谢工程
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产品关联
DOI
高影响因子
MOLECULES
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2018
·Vol. 23
·期 12
·3276
·
IF 3.098
Chuxin Liang,Chang Chen,Pengfei Zhou,Lv Xu,Jianhua Zhu,Jincai Liang,Jiachen Zi,Rongmin Yu
This study reported the inducing effect ofAspergillus flavusfungal elicitor on biosynthesis of terpenoid indole alkaloids (TIAs) inCatharanthus roseuscambial meristematic cells (CMCs) and its inducing mechanism. According to the results determined by HPLC and HPLC-MS/MS, the optimal condition of theA. flavuselicitor was as follows: after suspension culture ofC. roseusCMCs for 6 day, 25 mg/LA. flavusmycelium elicitor were added, and the CMC suspensions were further cultured for another 48 h. In this condition, the contents of vindoline, catharanthine, and ajmaline were 1.45-, 3.29-, and 2.14-times as high as those of the control group, respectively. Transcriptome analysis showed thatD4H,G10H,GES,IRS,LAMT,SGD,STR,TDC, andORCA3were involved in the regulation of this induction process. The results of qRT-PCR indicated that the increasing accumulations of vindoline, catharanthine, and ajmaline inC. roseusCMCs were correlated with the increasing expression of the above genes. Therefore,A. flavusfungal elicitor could enhance the TIA production ofC. roseusCMCs, which might be used as an alternative biotechnological resource for obtaining bioactive alkaloids.Keywords:Catharanthus roseus;cambial meristematic cells;Aspergillus flavus;terpenoid indole alkaloids;biosynthesis
研究领域:
植物生物技术
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植物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2015
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IF 2.729
Zhi Liu,Hai-Long Wu,Yong Li,Hui-Wen Gu,Xiao-Li Yin,Li-Xia Xie,Ru-Qin Yu
A novel chemometrics-assisted high performance liquid chromatography method coupled with diode array detector (HPLC–DAD) was proposed for the simultaneous determination of vincristine (VCR), vinblastine (VLB), vindoline (VDL), catharanthine (CAT) and yohimbine (YHB) in Catharanthus roseus ( C. roseus ) and human serum samples. With the second-order advantage of the alternating trilinear decomposition (ATLD) method, the resolution and rapid determination of five components of interest in complex matrices were performed, even in the present of heavy overlaps and unknown interferences. Therefore, multi-step purification was omitted and five components could be fast eluted out within 7.5 min under simple isocratic elution condition (acetonitrile/0.2% formic acid water, 37:63, v/v). Statistical parameters, such as the linear correlation coefficient ( R 2 ), root-mean-square error of prediction (RMSEP), limit of detection (LOD) and limit of quantitation (LOQ) had been calculated to investigate the accuracy and reliability of the method. The average recoveries of five vinca alkaloids ranged from 97.1% to 101.9% and 98.8% to 103.0% in C. roseus and human serum samples, respectively. The five vinca alkaloids were adequately determined with limits of detection (LODs) of 29.5–49.3 ng mL −1 in C. roseus and 12.4–27.2 ng mL −1 in human serum samples, respectively. The obtained results demonstrated that the analytical strategy provided a feasible alternative for synchronously monitoring the quality of raw herb and the concentration of blood drugs.
研究领域:
植物化学
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药物分析
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分析化学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2014
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IF 3.259
Junyan Wang,Minmin Huang,Haihong Hu,Lushan Yu,Su Zeng
The induction of drug-metabolising enzymes is being increasingly recognised for its clinical importance in drug research and development. In the present study, we used a pregnane X receptor (PXR)-mediated reporter gene assay to evaluate the activating effects of various food, herb, and horticultural plant constituents on the PXR and a UGT1A1 reporter gene DNA construct. The results showed that of 102 naturally occurring constituents tested, 50 activated the PXR signaling pathway and induced expression of the UGT1A1 -reporter gene DNA construct. Eleven constituents strongly induced gene expression (a response of >70% compared to that associated with rifampicin), and were further evaluated in in vitro experiments to confirm the induction of UGT1A1 mRNA and protein expression. The results suggest that foods and herbs containing these constituents should be consumed with caution to avoid undesirable drug–drug interactions with co-administered drugs that are substrates for UGT1A1.
研究领域:
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）