scholarly journals Effect of Enzyme Inhibitors on Terpene Trilactones Biosynthesis and Gene Expression Profiling in Ginkgo biloba Cultured Cells

2015 ◽  
Vol 10 (12) ◽  
pp. 1934578X1501001
Author(s):  
Lijia Chen ◽  
Hui Tong ◽  
Mingxuan Wang ◽  
Jianhua Zhu ◽  
Jiachen Zi ◽  
...  
Keyword(s):  
Ginkgo Biloba ◽  
Expression Profiling ◽  
Biosynthetic Pathway ◽  
Enzyme Inhibitors ◽  
Cultured Cells ◽  
Mevalonic Acid ◽  
Specific Enzyme ◽  
Mva Pathway ◽  
Terpene Trilactones ◽  
Highly Correlated

The biosynthetic pathway of terpene trilactones of Ginkgo biloba is unclear. In this present study, suspension cultured cells of G. biloba were used to explore the regulation of the mevalonic acid (MVA) and methylerythritol 4-phosphate (MEP) pathways in response to specific enzyme inhibitors (lovastatin and clomazone). The results showed that the biosynthesis of bilobalide was more highly correlated with the MVA pathway, and the biosynthesis of ginkgolides was more highly correlated with the MEP pathway. Meanwhile, according to the results, it could be speculated that bilobalide might be a product of ginkgolide metabolism.

Effect of Levopimaradiene on Terpene Trilactones Biosynthesis and Gene Expression Profiling in Ginkgo biloba Cells

2017 ◽  
Vol 12 (7) ◽  
pp. 1934578X1701200
Author(s):  
Jianhua Zhu ◽  
Pu Wang ◽  
Minghua Qian ◽  
Chuxin Liang ◽  
Jiachen Zi ◽  
...  
Keyword(s):  
Ginkgo Biloba ◽  
Expression Profiling ◽  
Biosynthetic Pathway ◽  
Mep Pathway ◽  
Ginkgolide B ◽  
Control Groups ◽  
Meristematic Cells ◽  
Qrt Pcr ◽  
Ginkgolide A ◽  
Terpene Trilactones

Ginkgolides (GKs) and Bilobalide (BB) are rare terpene trilactones obtained from Ginkgo biloba, but their biosynthetic pathway is still unclear. In this paper, effects of levopimaradiene (LP) on increasing the production of terpene trilactones of G. biloba dedifferentiated cells (DDCs) and cambial meristematic cells (CMCs) were reported. The productions of ginkgolide A (GA) and ginkgolide B (GB) were 1.61 and 1.32 folds larger than that of the control groups when G. biloba DDCs was treated with LP, and the productions of ginkgolide C (GC) and BB reached 234 and 161 μg L−1 after treated with LP for 60 h. The production of GA, GB, GC and BB was 2.03, 1.43, 1.22 and 1.19 folds larger than that of the control groups in LP-treated CMCs groups. The results demonstrated that BB could be produced from the methylerythritol 4-phosphate (MEP) pathway. qRT-PCR experiments showed that LP was a significant precursor manipulated the biosynthesis of terpene trilactones via affecting the transcript levels of several related genes in the MEP pathway.

scholarly journals Characterization and functional analysis of two novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes (GbHMGR2 and GbHMGR3) from Ginkgo biloba

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shen Rao ◽  
Xiangxiang Meng ◽  
Yongling Liao ◽  
Tian Yu ◽  
Jie Cao ◽  
...  
Keyword(s):  
Ginkgo Biloba ◽  
High Performance ◽  
Coenzyme A ◽  
Expression Patterns ◽  
Mevalonic Acid ◽  
Regulatory Elements ◽  
Promoter Regions ◽  
Mva Pathway ◽  
Cdna Sequences ◽  
Coenzyme A Reductase

Abstract Terpene trilactones (TTLs) are the main secondary metabolites of Ginkgo biloba. As one of the rate-limiting enzymes in the mevalonic acid (MVA) pathway of TTL biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyzes the 3-hydroxy-3-methylglutaryl coenzyme A to form MVA. In this study, two cDNA sequences of HMGR genes, namely, GbHMGR2 and GbHMGR3, were cloned from G. biloba. The protein sequences of GbHMGR2 and GbHMGR3, which contain several functional domains, were analyzed. Regulatory elements related to light, hormone, and stress response were detected in the promoter regions of GbHMGR2 and GbHMGR3. The catalytic activity of these genes was verified by a functional complement experiment in yeast. Quantitative real-time PCR (qRT-PCR) showed the distinct expression patterns of the two genes in different organs. The TTL contents in the organs were detected by high-performance liquid chromatography– evaporative light scattering detector. GbHMGR2 and GbHMGR3 were responded to cold, dark, methyl jasmonate (MJ), abscisic acid (ABA), salicylic acid (SA), and ethephon (Eth) treatments. The TTL contents were also regulated by cold, dark, MJ, ABA, SA, and Eth treatment. In conclusion, GbHMGR2 and GbHMGR3 may participate in the MVA pathway of TTL biosynthesis.

Quantitative GC-FID and UHPLC-DAD Evaluation of Bioactive Compounds Extracted from Ginkgo biloba

2020 ◽  
Vol 16 (7) ◽  
pp. 893-904
Author(s):  
Alessandra von Ahn ◽  
João Henrique Z. dos Santos
Keyword(s):  
Ginkgo Biloba ◽  
Extraction Efficiency ◽  
Extraction Methods ◽  
Ginkgo Biloba Extract ◽  
Previous Method ◽  
Array Detector ◽  
Ginkgolide B ◽  
Detection Techniques ◽  
Ginkgolide A ◽  
Terpene Trilactones

Background: The official compendium of the quantification of ginkgo flavonoids from Ginkgo biloba extract has been proposed using HPLC. The drawbacks of this technique appear to be due to the restricted efficiency in terms of the recovery results and suitability of the system for the quantification of these compounds. This study investigated the potential advantages and limitations of the development of efficient extraction methods for the recovery of flavonol glycosides (quercetin, kaempferol and isorhamnetin) and terpene trilactones (bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) using extraction, quantification and detection techniques, namely, GC-FID and UHPLC-DAD, which are alternatives to those techniques available in the literature. Methods: Two different extraction methodologies have been developed for the determination of flavonoids (quercetin, kaempferol and isorhamnetin) and terpene trilactones (bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) using ultra-high-pressure liquid chromatography coupled to a diode array detector and gas chromatography coupled to a flame ionization detector. Results: In this study, the Ginkgo biloba extract mass, hydrolysis preparation method (with or without reflux), and volume of the extraction solution seemed to affect the ginkgo flavonoid recovery. The UHPLC-based method exhibited higher extraction efficiency for ginkgo flavonoid quantification compared to the pharmacopoeial method. The developed method exhibited higher extraction efficiency for terpene quantification compared to the previous method that used extractive solution without pH adjustment, with less time of extraction and less amount of the sample and organic solvent aliquots. Conclusion: The UHPLC and GC analysis methods established in this study are both effective and efficient. These methods may improve the quality control procedures for ginkgo extract and commercial products available in today´s natural health product market. The results indicate that redeveloped extraction methods can be a viable alternative to traditional extraction methods.

Specific enzyme inhibitors in vitamin biosynthesis. Part II. Revised structures for some 8-substituted pyrido[2,3-d]pyrimidines

1974 ◽  
pp. 1225 ◽  
Author(s):  
Hamish C. S. Wood ◽  
Roger Wrigglesworth ◽  
David A. Yeowell ◽  
Frederick W. Gurney ◽  
B. Stuart Hurblert
Keyword(s):  
Enzyme Inhibitors ◽  
Specific Enzyme

scholarly journals Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 211 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin ◽  
Keizo Kanasaki ◽  
Daisuke Koya
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renal Fibrosis ◽  
Enzyme Inhibitors ◽  
Cultured Cells ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Critical Event ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Tgfβ Signaling ◽  
Converting Enzyme Inhibitors

Two class of drugs 1) angiotensin-converting enzyme inhibitors (ACEis) and 2) angiotensin II receptor blockers (ARBs) are well-known conventional drugs that can retard the progression of chronic nephropathies to end-stage renal disease. However, there is a lack of comparative studies on the effects of ACEi versus ARB on renal fibrosis. Here, we observed that ACEi ameliorated renal fibrosis by mitigating DPP-4 and TGFβ signaling, whereas, ARB did not show. Moreover, the combination of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), one of the substrates of ACE, with ACEi slightly enhanced the inhibitory effects of ACEi on DPP-4 and associated-TGFβ signaling. Further, the comprehensive miRome analysis in kidneys of ACEi+AcSDKP (combination) treatment revealed the emergence of miR-29s and miR-let-7s as key antifibrotic players. Treatment of cultured cells with ACEi alone or in combination with AcSDKP prevented the downregulated expression of miR-29s and miR-let-7s induced by TGFβ stimulation. Interestingly, ACEi also restored miR-29 and miR-let-7 family cross-talk in endothelial cells, an effect that is shared by AcSDKP suggesting that AcSDKP may be partially involved in the anti-mesenchymal action of ACEi. The results of the present study promise to advance our understanding of how ACEi regulates antifibrotic microRNAs crosstalk and DPP-4 associated-fibrogenic processes which is a critical event in the development of diabetic kidney disease.

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