scholarly journals AsWRKY44 represses the wound-induced sesquiterpene biosynthetic gene ASS1 expression in Aquilaria sinensis (Lour.) Gilg

Author(s):  
Pei-Wen Sun ◽  
Yan-Hong Xu ◽  
Cui-Cui Yu ◽  
Fei-Fei Lv ◽  
Xiao-Lin Tang ◽  
...  

Abstract Agarwood is derived from wounded Aquilaria trees and is widely used in traditional medicine, incense, and perfume. Sesquiterpenes are one of the main active components in agarwood and are known to be induced by wounding or injury. The molecular mechanism by which wounding leads to sesquiterpene formation remains largely unknown. ASS1 is one of key enzymes responsible for the biosynthesis of sesquiterpenes and is a pivotal jasmonate (JA)-responsive wound-inducible synthase. However, why ASS1 does not express in healthy trees and how its expression is induced as a result of wounding remains unexplored. Here, we report that ASS1 is a wound-induced gene with a promoter in which the 242-bp (-973 to -731bp) region is identified as the core sequence for responding to wound signals. AsWRKY44 binds directly to this region and represses ASS1 promoter activity. Downregulation or disruption of AsWRKY44 can relieve the inhibition and activate ASS1 expression. Further, it is found that in response to the exogenous MeJA, AsWRKY44 is degraded and the expression of ASS1 is significantly upregulated. These findings confirm AsWRKY44 is a crucial negative regulator involved in the regulation of wound-induced ASS1 transcription, which reveals the core mechanism of agarwood sesquiterpenes biosynthesis.

2018 ◽  
Vol 8 (2) ◽  
pp. 45
Author(s):  
Chrisye Yustitia Pelokang ◽  
Roni Koneri ◽  
Deidy Katili

Abstrak Tumbuhan obat merupakan tumbuhan yang menghasilkan satu atau lebih komponen aktif yang dipercaya oleh penduduk berkhasiat obat sehingga dimanfaatkan dalam pengobatan tradisional. Penelitian ini bertujuan untuk mengidentifikasi dan mengkaji spesies tumbuhan yang digunakan sebagai obat tradisional oleh Etnis Sangihe di Kepulauan Sangihe bagian Selatan, Sulawesi Utara. Pengambilan data dilakukan melalui wawancara terstruktur  yang diajukan kepada pengobat tradisional. Hasil penelitian menunjukkan adanya 38 spesies dari 25 famili tumbuhan yang dimanfaatkan sebagai tumbuhan obat oleh Etnis Sangihe bagian Selatan. Herba merupakan habitus tumbuhan yang banyak dimanfaatkan untuk bahan pengobatan. Bagian tumbuhan yang paling banyak digunakan sebagai obat yaitu daun. Cara pengolahan yang paling banyak digunakan adalah direbus. Jenis penyakit yang dapat diobati dengan tumbuhan obat sebanyak 22 jenis penyakit. Kata kunci: tumbuhan obat, obat tradisional, habitus, Kepulauan Sangihe Bagian Selatan Abstract             Medicinal plants are plants that produce one or more active components that are believed by local people as medicinal plants for traditional medicine practices. This study aimed to identify and to assess the plant species that used as traditional medicine by the Sangihe Ethnic in the Southern Sangihe Islands, North Sulawesi. Data collection was conducted by structured interviews to the indigenous medical practitioners. The results showed that 38 plant species from 25 plant families were used as medicinal plants by the Southern Sangihe Ethnic people. Herbs were plant habitus that were widely used for medicinal ingredients. The leaves were widely used as medicinal plant materials. Boiling was the most processing method for preparing medicinal herbs. There were 22 types of diseases that could be treated using medicinal plants. Keywords: medicinal plants, traditional medicine, habitus, Southern Sangihe Islands


2021 ◽  
Author(s):  
Xuhua Mo ◽  
Tobias A. M. Gulder

Over 30 biosynthetic gene clusters for natural tetramate have been identified. This highlight reviews the biosynthetic strategies for formation of tetramic acid unit for the first time, discussing the individual molecular mechanism in detail.


2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110167
Author(s):  
Xing-Pan Wu ◽  
Tian-Shun Wang ◽  
Zi-Xin Yuan ◽  
Yan-Fang Yang ◽  
He-Zhen Wu

Objective To explore the anti-COVID-19 active components and mechanism of Compound Houttuynia mixture by using network pharmacology and molecular docking. Methods First, the main chemical components of Compound Houttuynia mixture were obtained by using the TCMSP database and referring to relevant chemical composition literature. The components were screened for OB ≥30% and DL ≥0.18 as the threshold values. Then Swiss Target Prediction database was used to predict the target of the active components and map the targets of COVID-19 obtained through GeneCards database to obtain the gene pool of the potential target of COVID-19 resistance of the active components of Compound Houttuynia mixture. Next, DAVID database was used for GO enrichment and KEGG pathway annotation of targets function. Cytoscape 3.8.0 software was used to construct a “components-targets-pathways” network. Then String database was used to construct a “protein-protein interaction” network. Finally, the core targets, SARS-COV-2 3 Cl, ACE2 and the core active components of Compound Houttuyna Mixture were imported into the Discovery Studio 2016 Client database for molecular docking verification. Results Eighty-two active compounds, including Xylostosidine, Arctiin, ZINC12153652 and ZINC338038, were screened from Compound Houttuyniae mixture. The key targets involved 128 targets, including MAPK1, MAPK3, MAPK8, MAPK14, TP53, TNF, and IL6. The HIF-1 signaling, VEGF signaling, TNF signaling and another 127 signaling pathways associated with COVID-19 were affected ( P < 0.05). From the results of molecular docking, the binding ability between the selected active components and the core targets was strong. Conclusion Through the combination of network pharmacology and molecular docking technology, this study revealed that the therapeutic effect of Compound Houttuynia mixture on COVID-19 was realized through multiple components, multiple targets and multiple pathways, which provided a certain scientific basis of the clinical application of Compound Houttuynia mixture.


1999 ◽  
Vol 80 (1-2) ◽  
pp. 110-116 ◽  
Author(s):  
S Vimala ◽  
A W Norhanom ◽  
M Yadav

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 58
Author(s):  
Ke Xu ◽  
Hao Zhou ◽  
Chengxiao Han ◽  
Zhong Xu ◽  
Jinmei Ding ◽  
...  

In mammals, Myostatin (MSTN) is a known negative regulator of muscle growth and development, but its role in birds is poorly understood. To investigate the molecular mechanism of MSTN on muscle growth and development in chickens, we knocked out MSTN in chicken fetal myoblasts (CFMs) and sequenced the mRNA transcriptomes. The amplicon sequencing results show that the editing efficiency of the cells was 76%. The transcriptomic results showed that 296 differentially expressed genes were generated after down-regulation of MSTN, including angiotensin I converting enzyme (ACE), extracellular fatty acid-binding protein (EXFABP) and troponin T1, slow skeletal type (TNNT1). These genes are closely associated with myoblast differentiation, muscle growth and energy metabolism. Subsequent enrichment analysis showed that DEGs of CFMs were related to MAPK, P13K/AKT, and STAT3 signaling pathways. The MAPK and P13K/AKT signaling pathways are two of the three known signaling pathways involved in the biological effects of MSTN in mammals, and the STAT3 pathway is also significantly enriched in MSTN knock out chicken leg muscles. The results of this study will help to understand the possible molecular mechanism of MSTN regulating the early differentiation of CFMs and lay a foundation for further research on the molecular mechanism of MSTN involvement in muscle growth and development.


2021 ◽  
Author(s):  
Jing Yang ◽  
Chao-Tao Tang ◽  
Ruiri Jin ◽  
Bixia Liu ◽  
Peng Wang ◽  
...  

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.


2021 ◽  
Author(s):  
Xuedong An ◽  
LiYun Duan ◽  
YueHong Zhang ◽  
De Jin ◽  
Shenghui Zhao ◽  
...  

Abstract BackgroundOur previous randomized, double-blind, placebo-controlled, multi-center clinical study showed that Compound Danshen Dripping Pills (CDDP) had a significant and safe effect in the treatment of diabetic retinopathy (DR), but its mechanism is still unclear, which we would explain based on network pharmacology and molecular docking.MethodThe active ingredients of CDDP (composed of Panax notoginseng, Salvia miltiorrhiza Bge., and Borneol) were searched in the TCMSP database. The validated target and Smiles number of the active ingredient are queried through the PubChem database, and the predicted target of the active ingredient is obtained through the Swisstarget Prediction database. The Drugbank, TTD, and DisGeNET databases were retrieved to obtain the related targets of DR. The core targets were obtained by the cluster analysis function of Cytoscape, and then the Protein-Protein Interaction was performed. The GO and KEGG signal pathways were enriched and clustered in David database. The potential active components and targets were docking with Autodock Vina, and the results were visualized by PyMOL.Result51 active components and 922 validation and prediction targets of CDDP, 715 targets of DR and 154 co-targets were obtained. Cluster analysis showed that there were two clusters, a total of 64 targets. Go and KEGG signal pathway enrichment analysis showed that the top 20 mainly included TNF and HIF-1 signaling pathway. In GO analysis, BP mainly includes positive regulation of smooth muscle cell proliferation and response to hypoxia, CC mainly includes extracellular space and extracellular domain, MF mainly includes protein binding and protein binding recognition. In KEGG database, the key genes in the TNF signaling pathway were TNF, NFkB and VEGF, in HIF-1 signaling pathway were the IL-6, STAT3, HIF1A and VEGF. Molecular docking results showed that all components of CDDP had a certain docking ability with TNF, NFkB, VEGF, IL-6, STAT3 and HIF1A, which of Asiatic acid and Salvianolic acid j was the strongest.Conclusion Based on the network pharmacology and molecular docking, the core active components of CDDP, mainly including Asiatic acid and Salvianolic acid j, which may play a role in regulating cell proliferation and response to inflammation and hypoxia by regulating the binding and recognition of intracellular and extracellular proteins, that is, mainly through TNF signaling pathway and HIF-1 signaling pathway.


1991 ◽  
Vol 11 (9) ◽  
pp. 4297-4305
Author(s):  
C Jones ◽  
K A Lee

The cellular factors E4F and ATF-2 (a member of the activating transcription factor [ATF] family) bind to common sites in the adenovirus E4 promoter and have both been suggested to mediate transcriptional activation by the viral E1A protein. To assess the role of E4F, we have introduced mutations into the E4F/ATF binding sites of the E4 promoter and monitored promoter activity in HeLa cells. We find that the core motif (TGACG) of the E4F/ATF binding site is important for E4 promoter activity. However, a point mutation adjacent to the core motif that reduces E4F binding (but has no effect on ATF binding) has no effect on E4 promoter activity. Together with previous results, these findings indicate that there are at least two cellular factors (a member of the ATF family and E4F) that can function with E1A to induce transcription of the E4 promoter. We also find that certain mutations strongly reduce E4 transcription in vivo but have no effect on ATF-2 binding in vitro. These results are therefore incompatible with the possibility that (with respect to members of the ATF family) ATF-2 alone can function with E1A to transactivate the E4 promoter in HeLa cells.


2021 ◽  
Author(s):  
Xi Cen ◽  
Yan Wang ◽  
LeiLei Zhang ◽  
XiaoXiao Xue ◽  
Yan Wang ◽  
...  

Abstract BackgroundType 2 diabetes mellitus (T2DM) is regarded as Pi Dan disease in traditional Chinese medicine (TCM). Dahuang Huanglian Xiexin Decoction (DHXD), a classical TCM formula, has been used for treating Pi Dan disease in clinic, its pharmacological mechanism has not been elucidated. MethodsThis study used network pharmacological analysis and molecular docking approach to explore the mechanism of DHXD on T2DM. Firstly, the compounds in DHXD were obtained from TCMSP and TCMID databases, the potential targets were determined based on TCMSP and UniProt databases. Next, Genecards, Digenet and UniProt databases were used to identify the targets of T2DM. Then, the protein-protein interaction (PPI) network was established with overlapping genes of T2DM and compounds, and the core targets in the network were identified and analyzed. Then, the David database was used for GO and KEGG enrichment analysis. Finally, the target genes were selected and the molecular docking was completed by Autodock software to observe the binding level of active components with target genes.ResultsA total of 397 related components and 128 overlapping genes were identified. After enrichment analysis, it was found that HIF-1, TNF, IL-17 and other signaling pathways, as well as DNA transcription, gene expression, apoptosis and other cellular biological processes had the strongest correlation with the treatment of T2DM by DHXD, and most of them occurred in the extracellular space, plasma membrane and other places, which were related to enzyme binding and protein binding. In addition, 42 core genes of DHXD, such as VEGFA, TP53 and MAPK1, were considered as potential therapeutic targets, indicating the potential mechanism of DHXD on T2DM. Finally, the results of molecular docking showed that HIF-1 pathway had strong correlation with the target genes INSR and GLUT4, quercetin and berberine had the strongest binding power with them respectively.ConclusionThis study summarized the main components of DHXD in the treatment of T2DM, identified the core genes and pathways, and systematically analyzed the interaction of related targets, trying to lay the foundation for clarifying the potential mechanism of DHXD on T2DM, so as to carry out further research in the future.


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