Inhibition Of Metabolizing Enzymes Research Articles

Antidiabetic and Antigout Properties of the Ultrasound-Assisted Extraction of Total Biflavonoids from Selaginella doederleinii Revealed by In Vitro and In Silico Studies

In this study, the extraction, purification and metabolic enzyme inhibition potential of Selaginella doederleinii were investigated. In order to extract the total biflavonoids from S. doederleinii (SDTBs), the optimum extraction process was obtained by optimizing the ultrasonic extraction parameters using response-surface methodology. This resulted in a total biflavonoid content of 22.26 ± 0.35 mg/g. Purification of the S. doederleinii extract was carried out using octadecylsilane (ODS), and the transfer rate of the SDTBs was 82.12 ± 3.48% under the optimum purification conditions. We determined the effect of the SDTBs on α-glucosidase (AG), α-amylase and xanthine oxidase (XOD) and found that the SDTBs had an extremely potent inhibitory effect on AG, with an IC50 value of 57.46 μg/mL, which was much lower than that of the positive control. Meanwhile, they also showed significant inhibition of XOD and α-amylase, with IC50 values of 289.67 μg/mL and 50.85 μg/mL, respectively. In addition, molecular docking studies were carried out to understand the nature of the action of the biflavonoids on AG and XOD. The results showed that robustaflavone had the lowest binding energy to AG (−11.33 kcal/mol) and XOD (−10.21 kcal/mol), while, on the other hand, amentoflavone showed a good binding affinity to AG (−10.40 kcal/mol) and XOD (−9.962 kcal/mol). Moreover, molecular dynamics simulations verified the above results.

Therapeutic modulation of ROCK overcomes metabolic adaptation of cancer cells to OXPHOS inhibition and drives synergistic anti-tumor activity.

Genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer. Previously, we and others have identified that SMARCA4-mutant lung cancers are highly dependent on oxidative phosphorylation (OXPHOS). Despite initial excitements, therapeutics targeting metabolic pathways such as OXPHOS have largely been disappointing due to rapid adaptation of cancer cells to inhibition of single metabolic enzymes or pathways, suggesting novel combination strategies to overcome adaptive responses are urgently needed. Here, we performed a functional genomics screen using CRISPR-Cas9 library targeting genes with available FDA approved therapeutics and identified ROCK1/2 as a top hit that sensitizes cancer cells to OXPHOS inhibition. We validate these results by orthogonal genetic and pharmacologic approaches by demonstrating that KD025 (Belumosudil), an FDA approved ROCK inhibitor, has highly synergistic anti-cancer activity in vitro and in vivo in combination with OXPHOS inhibition. Mechanistically, we showed that this combination induced a rapid, profound energetic stress and cell cycle arrest that was in part due to ROCK inhibition-mediated suppression of the adaptive increase in glycolysis normally seen by OXPHOS inhibition. Furthermore, we applied global phosphoproteomics and kinase-motif enrichment analysis to uncover a dynamic regulatory kinome upon combination of OXPHOS and ROCK inhibition. Importantly, we found converging phosphorylation-dependent regulatory cross-talk by AMPK and ROCK kinases on key RHO GTPase signaling/ROCK-dependent substrates such as PPP1R12A, NUMA1 and PKMYT1 that are known regulators of cell cycle progression. Taken together, our study identified ROCK kinases as critical mediators of metabolic adaptation of cancer cells to OXPHOS inhibition and provides a strong rationale for pursuing ROCK inhibitors as novel combination partners to OXPHOS inhibitors in cancer treatment.

Optimizing phlorotannins extraction from Fucus vesiculosus using Box-Behnken design: Unveiling techniques for enhanced antioxidant activity and metabolic enzyme inhibition

Phlorotannins, phenolic compounds found in brown macroalgae, exhibit potential bioactive effects. This study evaluated the extraction of phlorotannins from Fucus vesiculosus using conventional and ultrasound-assisted extraction (UAE) methods, focusing on solvent-material ratio, solvent concentration, extraction time, and sonication power for UAE. The experiments, designed using a Box-Behnken design, measured total phlorotannin content (TPhC), DPPH, FRAP, and ABTS. The conventional method, under optimal conditions, produced TPhC, DPPH, FRAP, and ABTS values of 512.25 ± 14.26 mg PGE/100 g, 29.70 ± 1.40 mg TE/100 g, 589.57 ± 15.06 mg TE/100 g, and 332.73 ± 31.03 mg TE/100 g, respectively. The UAE method, under its optimal conditions, yielded higher values: 954.00 ± 33.65 mg PGE/100 g, 146.35 ± 3.30 mg TE/100 g, 1037.61 ± 32.93 mg TE/100 g, and 809.95 ± 46.58 mg TE/100 g. The extracts were tested for inhibitory effects on α-amylase and α-glucosidase, with the purified UAE extract showing greater inhibition of α-amylase (IC50 = 7.06 ± 0.67 μg/mL) compared to acarbose (IC50 = 14.63 ± 0.28 μg/mL). For α-glucosidase, acarbose had higher activity (IC50 = 11.54 ± 0.04 μg/mL) than the UAE purified extract (IC50 = 15.04 ± 0.07 μg/mL). UHPLC-qTOF-MS analysis identified various phlorotannin derivatives, with Tetrafucotetraphlorethol (m/z 993) only in the UAE purified extract. This study concludes that purified phlorotannin extract from UAE can potentially regulate α-amylase and α-glucosidase, enzymes linked to metabolic disorders like diabetes and obesity.

Investigating the Diverse Therapeutic Potential of Hypericum triquetrifolium Aerial Parts in Palestine: Ranging from Examining Metabolic Enzyme Inhibition To Neuroprotective Effects

Investigating the Diverse Therapeutic Potential of Hypericum triquetrifolium Aerial Parts in Palestine: Ranging from Examining Metabolic Enzyme Inhibition To Neuroprotective Effects

Synthesis, fluorescence, enzymes effects, and evaluation of tetrahydroxy substituted zinc phthalocyanine as multitarget metabolic enzyme inhibitors with molecular docking: the biochemistry-oriented drug design

Synthesis, fluorescence, enzymes effects, and evaluation of tetrahydroxy substituted zinc phthalocyanine as multitarget metabolic enzyme inhibitors with molecular docking: the biochemistry-oriented drug design

NAD+ metabolic enzyme inhibitor as radiosensitizer for malignant meningioma and its modulation of P53 expression.

Surgical resection followed by radiotherapy (RT) is recommended for malignant meningioma but poor outcome is unavoidable. To improve the efficacy of RT in malignant meningioma, a targeted radiosensitizer could be added. Nicotinamide phosphoribosyltransferase (NAMPT), highly expressed in high-grade meningiomas may have a role in determining the radioresponse. Here, we evaluated the impact of NAMPT inhibition on radiosensitivity in malignant meningioma in vivo and in vitro. IOMM-Lee and TTMM705 cells were treated with NAMPT inhibition (FK866 or shRNA NAMPT) before irradiation. The subsequent clonogenic assay demonstrated significantly increased radiosensitivity. Combination treatment with FK866 and irradiation significantly increased the number of G2/M-phase cells, the percentage of apoptotic cells and the γ-H2A.X level compared to FK866 or RT alone. We examined the effect of NAMPT inhibition on NMI and p53 expression in IOMM-Lee and TTMM705 cells. NAMPT inhibition by FK866 and shRNA treatment increased NMI, p53, CDKN1A and BAX expression. Additionally, we assessed the efficacy of FK866/RT combination treatment in vivo. The combination treatment exhibited increased antitumor efficacy compared to either treatment alone. The Ki-67 level was significantly lower and the p53 and γ-H2A.X level was significantly higher in the combination treatment group than in any of the other three groups. In conclusion, these results indicate that FK866 improves radiosensitivity in malignant meningioma, an effect that may be attributed to the increase in p53 expression.

Determination of in vitro Antioxidant, Anticholinergic and Antiepileptic Activities of Some Aromatic Plant Extracts

Medicinal and aromatic plants such as Crocus cancellatus, Scilla Siberica subsp. armena, Juniperus oxycedrus subsp. oxycedrus and Anthriscus nemorosa have many different biological activities. While antioxidants are significant in preventing many diseases, inhibition of metabolic enzymes is also important in preventing many significant diseases. In this study, antioxidant activities of water, ethanol, and dichloromethane extracts of four different medicinal and aromatic plant species were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and 2,20-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS·+) radical scavenging and Cu2+, Fe+3, and Fe3+-2,4,6-tris(2-pyridyl)-S-triazine (TPTZ) reducing assays. Standard antioxidants (BHA, BHT, Trolox, α-Tocopherol) were used in antioxidant assays, and the results were evaluated according to these standards. Enzyme inhibition studies were performed with metabolic enzymes acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I and II isoenzymes. The ethanol extract of A. nemorosa showed the highest activity in DPPH assay (IC50: 17.36 µg mL-1). In the ABTS assay, the ethanol extract of A. nemorosa plant showed the highest activity (IC50: 7.02 µg mL-1). In the Fe3+ reducing assay, the dichloromethane extract of A. nemorosa showed the highest activity (1.96±0.060 µg mL-1). In the Cu2+ reducing assay, the dichloromethane extract of J. oxycedrus showed the highest activity (1.773±0.066 µg mL-1). In the Fe3+-TPTZ reducing assay, the ethanol extract of S. siberica showed the highest activity (1.256±0.011 µg mL-1). In the enzyme inhibition results, it was determined that all plants and all extracts inhibited the enzymes studied. As a result of this study, it was determined that these four medicinal and aromatic plants have high biological and antioxidant activities.

Investigation of Some Metabolic Enzyme Inhibition Properties of Novel Chalcone‐Cu Complexes

AbstractFourteen novel Chalcone‐Cu complexes were effectively synthesized in this work. The newly synthesized Chalcone‐Cu complexes were assessed for their effects on human carbonic anhydrase isoenzymes I and II, acetylcholinesterase enzymes, and antioxidant activity. The intricate compounds exhibited Ki values ranging from 41.65–190.42 nM against hCA I, 15.79–259.07 nM against hCA II, and 14.36–175.73 nM against AChE enzymes. These complexes demonstrated potent inhibitory profiles against the specified metabolic enzymes, surpassing the inhibitory effects of acetazolamide (for hCA I and II) and tacrine (for AChE). The antioxidant properties of the compounds were assessed using DPPH and ABTS radical scavenging assays, revealing that the complexes had moderate to high efficacy in neutralizing free radicals. All complexes underwent molecular docking experiments. Compounds 14, 22, and 23 yielded the highest docking scores. Compound 14 demonstrated a docking score of −6.414 kcal/mol against hCAI, whereas compound 23 attained a docking score of −6.697 kcal/mol against hCA II. Compound 22 exhibited the most favorable docking score of −9.645 kcal/mol against AChE. The acquired results have the potential to help towards the development of new drugs containing Cu complex structures for the treatment of prevalent ailments such as glaucoma and Alzheimer's diseases.

Synthesis, Molecular Docking, Some Metabolic Enzyme Inhibition Properties, and Antioxidant Activity Studies of 1,4-Naphthoquinones

Synthesis, Molecular Docking, Some Metabolic Enzyme Inhibition Properties, and Antioxidant Activity Studies of 1,4-Naphthoquinones

Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials

An important characteristic of cancer is aberrant metabolism. Drug resistance, cancer stem cells, metastasis and tumorigenesis are all significantly impacted by abnormal cancer metabolism, which includes enhanced anabolic pathways and aerobic glycolysis. The Hippo pathway, Myc and PI3K/AKT are recognized oncogenic signaling networks that control the expression of metabolic genes and increase the level of activity of metabolic enzymes. On the other hand, abnormal metabolic pathways result in disruptions to the internal signal transduction pathways of cells, providing energy, building blocks and redox capabilities necessary for uncontrolled cancer cell proliferation. Studies and clinical trials are being carried out to investigate the impact of minute substances or dietary modifications, such as calorie restriction, fasting and intermittent fasting, on the inhibition of metabolic enzymes. The metabolic phenotypes of malignancies are remarkably diverse, much like genetic variability. Genetic abnormalities and a variety of signals found in the tumor microenvironment contribute to this variability. Therefore, one of the main objectives of contemporary cancer therapies is to overcome metabolic plasticity. This overview explains the relationships between biochemical and pathways of signaling and emphasizes recent research on the metabolic properties of cancer. We also present fresh justifications for the upcoming class of medications that target cancer metabolism. This is an overview of our latest studies on the progress of nanomedicine and disease detection at the tiny level of nano-bio interactions between biological systems and nanoparticles. Significant progress in the field of nanomedicine has been accomplished in the last 20 years. However, the absence of a thorough knowledge of nano-bio interactions in the clinical situation makes it difficult to significantly improve overall patient survival with nanomedicine.

Synthesis novel N,S-substituted nitrobutadiene derivatives: some metabolic enzyme inhibition properties and antioxidant activities and in silico ADMET and molecular docking studies

Synthesis novel N,S-substituted nitrobutadiene derivatives: some metabolic enzyme inhibition properties and antioxidant activities and in silico ADMET and molecular docking studies

Ultrasound-Assisted Acidic Natural Deep Eutectic Solvent as a New Strategy for Extracting Seabuckthorn Leaf Phenolics: Process Optimization, Compositional Identification, and Metabolic Enzyme Inhibition Capacity

Ultrasound-Assisted Acidic Natural Deep Eutectic Solvent as a New Strategy for Extracting Seabuckthorn Leaf Phenolics: Process Optimization, Compositional Identification, and Metabolic Enzyme Inhibition Capacity

Traveling wave solution and the stability of critical points of an enzyme-inhibitor system under diffusion effects: with special reference to dimer molecule

Enzymes are absolutely essential biological catalysts in human body that catalyze all cellular processes in physiological network. However, there are certain low molecular weight chemical compounds known as inhibitors, that reduce or completely inhibit the enzyme catalytic activity. Mathematical modeling plays a key role in the control and stability of metabolic enzyme inhibition. Enzyme stability is an important issue for protein engineers, because of its great importance and impact on optimal utility of material in biological tissues. In this outlook, we have first determined the existence of traveling wave solution for the enzyme-inhibitor system and then emphasized the stability of critical points that arise in the reactions. The study of traveling wave solution of an enzyme-inhibitor system with reaction diffusion equations involve quite complex mathematical analysis. The results obtained in this model indicate that the traveling wave solution may give a well explained method for improving enzyme kinetic stability. The present study will be helpful in understanding the stability of critical points of an enzyme-inhibitor system to give an idea about the inhibition of less stable enzymes. Moreover, the role of diffusion on the enzyme activity has been exhaustively discussed using mathematical tools related to eigen values and eigen function analysis.

Synthesis, characterization, and computational study of novel carvacrol-based 2-aminothiol and sulfonic acid derivatives as metabolic enzyme inhibitors

Eight new 2-aminothiols (69–96%) and three new sulfonic acids (51–76%) were synthesized and characterized by NMR and HRMS spectra. This study presents the inhibitory effects of a series of novel carvacrol-based 2-aminothiol and sulfonic acid derivatives (3a-f,4a-c) against human carbonic anhydrase I and II isozymes (hCA I and II) acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glycosidase. Ki values were calculated as 12.52±3.61–335.65±60.56 nM for hCA I, 12.20±3.59–389.69±119.41 nM for hCA II, 1.79±0.56–84.86±23.34 nM for AChE, 6.57±2.54–88.05±21.05 nM for BChE and 14.63±4.76–116.39±33.70 nM α-glucosidase enzymes. Also, the inhibition effects of novel carvacrol-based 2-aminothiol (3a-h) and sulfonic acid derivatives (4a-c) were compared to standard and clinically used inhibitors of acetazolamide, Tacrine and acarbose, respectively. Molecular modeling studies of novel compounds, docking scores, and free binding energies were calculated. The activity results of the compounds were found to be compatible with the docking scores. Molecular dynamics studies were conducted with the best activity against CA I and CA II compounds, 4b (IC50: 4.76 nM) and 4a (IC50: 4.36 nM), respectively. In Dynamic Simulation studies, it was observed that the compounds remained stable at the active sites of the proteins.

Oncogenic Fatty Acid Metabolism Rewires Energy Supply Chain in Gastric Carcinogenesis

Background & AimsGastric carcinogenesis develops within a sequential carcinogenic cascade from pre-cancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can drive the process. Metabolic reprogramming is considered a key mechanism for cancer cell growth and proliferation. However, it remains unclear how metabolic changes contribute to the progression of metaplasia to dysplasia. We have examined metabolic dynamics during gastric carcinogenesis using a novel mouse model that induces Kras activation in zymogen-secreting chief cells. MethodsWe generated a Gif-rtTA;TetO-Cre;KrasG12D (GCK) mouse model which continuously induces active Kras expression in chief cells following doxycycline treatment. Histological examination and imaging mass spectrometry were performed in the GCK mouse stomachs at 2 to 14 weeks after doxycycline treatment. Mouse and human gastric organoids were used for metabolic enzyme inhibitor treatment. The GCK mice were treated with a stearoyl-CoA desaturase (SCD) inhibitor to inhibit the fatty acid desaturation. Tissue microarrays were used to assess the SCD expression in human gastrointestinal cancers. ResultsThe GCK mice developed metaplasia and high-grade dysplasia within 4 months. Metabolic reprogramming from glycolysis to fatty acid metabolism occurred during metaplasia progression to dysplasia. Altered fatty acid desaturation through SCD produces a novel Eicosenoic acid, which fuels dysplastic cell hyperproliferation and survival. The SCD inhibitor killed both mouse and human dysplastic organoids and selectively targeted dysplastic cells in vivo. SCD was upregulated during carcinogenesis in human gastrointestinal cancers. ConclusionsActive Kras expression only in gastric chief cells drives the full spectrum of gastric carcinogenesis. Also, oncogenic metabolic rewiring is an essential adaptation for high energy demand in dysplastic cells.

PpGpp accumulation reduces the expression of the global nitrogen homeostasis-modulating NtcA regulon by affecting 2-oxoglutarate levels

The cyanobacterium Synechococcus elongatus PCC 7942 accumulates alarmone guanosine tetraphosphate (ppGpp) under stress conditions, such as darkness. A previous study observed that artificial ppGpp accumulation under photosynthetic conditions led to the downregulation of genes involved in the nitrogen assimilation system, which is activated by the global nitrogen regulator NtcA, suggesting that ppGpp regulates NtcA activity. However, the details of this mechanism have not been elucidated. Here, we investigate the metabolic responses associated with ppGpp accumulation by heterologous expression of the ppGpp synthetase RelQ. The pool size of 2-oxoglutarate (2-OG), which activates NtcA, is significantly decreased upon ppGpp accumulation. De novo 13C-labeled CO2 assimilation into the Calvin-Benson-Bassham cycle and glycolytic intermediates continues irrespective of ppGpp accumulation, whereas the labeling of 2-OG is significantly decreased under ppGpp accumulation. The low 2-OG levels in the RelQ overexpression cells could be because of the inhibition of metabolic enzymes, including aconitase, which are responsible for 2-OG biosynthesis. We propose a metabolic rearrangement by ppGpp accumulation, which negatively regulates 2-OG levels to maintain carbon and nitrogen balance.

Physiologically-based pharmacokinetic model of sparsentan to evaluate drug-drug interaction potential.

Sparsentan is a dual endothelin/angiotensin II receptor antagonist indicated to reduce proteinuria in patients with primary IgA nephropathy at high risk of disease progression. Invitro data indicate that sparsentan is likely to inhibit or induce various CYP enzymes at therapeutic concentrations. Sparsentan as a victim and perpetrator of CYP3A4 mediated drug-drug interactions (DDIs) has been assessed clinically. A mechanistic, bottom-up, physiologically-based pharmacokinetic (PK) model for sparsentan was developed based on invitro data of drug solubility, formulation dissolution and particle size, drug permeability, inhibition and induction of metabolic enzymes, and P-glycoprotein (P-gp) driven efflux. The model was verified using clinical PK data from healthy adult volunteers administered single and multiple doses in the fasted and fed states for a wide range of sparsentan doses. The model was also verified by simulation of clinically observed DDIs. The verified model was then used to test various DDI simulations of sparsentan as a perpetrator and victim of CYP3A4 using an expanded set of inducers and inhibitors with varying potency. Additional perpetrator and victim DDI simulations were performed using probes for CYP2C9 and CYP2C19. Simulations were conducted to predict the effect of complete inhibition of P-gp inhibition on sparsentan absorption and clearance. The predictive simulations indicated that exposure of sparsentan could increase greater than two-fold if co-administered with a strong CYP3A4 inhibitor, such as itraconazole. Other potential DDI interactions as victim or perpetrator were all within two-fold of control. The effect of complete P-gp inhibition on sparsentan PK was negligible.

The immunometabolic ecosystem in cancer.

Our increased understanding of how key metabolic pathways are activated and regulated in malignant cells has identified metabolic vulnerabilities of cancers. Translating this insight to the clinics, however, has proved challenging. Roadblocks limiting efficacy of drugs targeting cancer metabolism may lie in the nature of the metabolic ecosystem of tumors. The exchange of metabolites and growth factors between cancer cells and nonmalignant tumor-resident cells is essential for tumor growth and evolution, as well as the development of an immunosuppressive microenvironment. In this Review, we will examine the metabolic interplay between tumor-resident cells and how targeted inhibition of specific metabolic enzymes in malignant cells could elicit pro-tumorigenic effects in non-transformed tumor-resident cells and inhibit the function of tumor-specific T cells. To improve the efficacy of metabolism-targeted anticancer strategies, a holistic approach that considers the effect of metabolic inhibitors on major tumor-resident cell populations is needed.

Tryptophan metabolism regulates inflammatory macrophage polarization as a predictive factor for breast cancer immunotherapy

Metabolic reprogramming plays a pivotal role in regulating macrophage polarization and function. However, the impact of macrophage tryptophan metabolism on polarization within the breast cancer microenvironment remains elusive. In this study, we used single-cell transcriptome analysis and found that macrophages had the highest tryptophan metabolic activity in breast cancer, melanoma, and head and neck squamous cell carcinoma (HNSC). Further analysis revealed that the tryptophan metabolic activity of macrophages was positively correlated with the M1 macrophage scores in breast cancer. Pancancer analysis found positive correlations between tryptophan metabolism and the M1 macrophage score in almost all tumor types. Spatial transcriptome analysis revealed higher tryptophan metabolism in regions with higher M1 macrophage score in breast cancer tissues. Immune infiltration analysis revealed that the high tryptophan metabolism group exhibited a higher immune score, an increased proportion of CD8+ T cells, augmented cytolytic activity mediated by CD8+ T cells, and elevated expression of immune checkpoint molecules. Spatial immunophenotype cohort analysis exhibited that breast cancer patients expected to respond to immunotherapy had stronger tryptophan metabolism, with a 73.8 % area under the ROC curve. Single-cell transcriptome analysis of the immunotherapy cohort found that patients responding to immunotherapy had higher macrophage tryptophan metabolism prior to treatment initiation. Finally, in vitro experiments demonstrated elevated expression of tryptophan metabolic enzymes in M1 macrophages. Moreover, tryptophan facilitated the expression of M1 polarization markers, whereas inhibitors of tryptophan metabolic enzymes, such as NLG919, LM10, and Ro 61–8048, inhibited the expression of M1 polarization markers. In conclusion, this study identified a dual role for macrophage tryptophan metabolism in breast cancer; on the one hand, it promotes macrophage M1 polarization, while on the other hand, it serves as a promising predictor for the effectiveness of immunotherapy in breast cancer.

Eleusine indica Cytochrome P450 and Glutathione S-Transferase Are Linked to High-Level Resistance to Glufosinate.

Eleusine indica has become a global nuisance weed and has evolved resistance to glufosinate. The involvement of target-site resistance (TSR) in glufosinate resistance in E. indica has been elucidated, while the role of nontarget-site resistance (NTSR) remains unclear. Here, we identified a glufosinate-resistant (R) population that is highly resistant to glufosinate, with a resistance index of 13.5-fold. Molecular analysis indicated that the resistance mechanism of this R population does not involve TSR. In addition, pretreatment with two known metabolic enzyme inhibitors, the cytochrome P450 (CYP450) inhibitor malathion and the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl), increased the sensitivity of the R population to glufosinate. The results of subsequent RNA sequencing (RNA-seq) and quantitative real-time PCR (RT-qPCR) suggested that the constitutive overexpression of a GST gene (GSTU3) and three CYP450 genes (CYP94s and CYP71) may play an important role in glufosinate resistance. This study provides new insights into the resistance mechanism of E. indica.