Amarogentin, a secoiridoid glycoside, activates AMP- activated protein kinase (AMPK) to exert beneficial vasculo-metabolic effects

Potunuru, Uma Rani; Priya, K. Vishnu; Varsha, M.K.N. Sai; Mehta, Nikunj; Chandel, Shivam; Manoj, Narayanan; Raman, Thiagarajan; Manikandan, R.; Gromiha, M. Michael; Dixit, Madhulika

doi:10.1016/j.bbagen.2019.05.008

Cited by 19 publications

(9 citation statements)

References 60 publications

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“…Amarogentin is a kind of secoiridoid-type compound that can be found in Gentiana lutea , Swertia japonica , Gentianella nitida , and Swertia chirayita [ 28 – 30 ]. It has been reported to possess various activities, such as anti-inflammatory, immunomodulatory, antioxidative stress, and antidiabetic effects [ 31 – 33 ]. Herein, the antiaging, neuroprotective, and neuritogenic effects and the underlying mechanism of the natural bioactive product, amarogentin, which possesses antioxidative stress potential for treatment neurodegenerative disease, will be reported.…”

Section: Introductionmentioning

confidence: 99%

Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress

Disasa

Cheng

Manzoor

et al. 2020

Oxidative Medicine and Cellular Longevity

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In the present study, the replicative lifespan assay of yeast was used to guide the isolation of antiaging substance from Gentiana rigescens Franch, a traditional Chinese medicine. A compound with antiaging effect was isolated, and the chemical structure of this molecule as amarogentin was identified by spectral analysis and compared with the reported data. It significantly extended the replicative lifespan of K6001 yeast at doses of 1, 3, and 10 μM. Furthermore, amarogentin improved the survival rate of yeast under oxidative stress by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and these enzymes’ gene expression. In addition, this compound did not extend the replicative lifespan of sod1, sod2, uth1, and skn7 mutants with K6001 background. These results suggested that amarogentin exhibited antiaging effect on yeast via increase of SOD2, CAT, GPx gene expression, enzyme activity, and antioxidative stress. Moreover, we evaluated antioxidant activity of this natural products using PC12 cell system, a useful model for studying the nervous system at the cellular level. Amarogentin significantly improved the survival rate of PC12 cells under H2O2-induced oxidative stress and increased the activities of SOD and SOD2, and gene expression of SOD2, CAT, GPx, Nrf2, and Bcl-x1. Meanwhile, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) of PC12 cells were significantly reduced after treatment of the amarogentin. These results indicated that antioxidative stress play an important role for antiaging and neuroprotection of amarogentin. Interestingly, amarogentin exhibited neuritogenic activity in PC12 cells. Therefore, the natural products, amarogentin from G. rigescens with antioxidant activity could be a good candidate molecule to develop drug for treating neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress

Disasa

Cheng

Manzoor

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Recently, plant-derived extracts or compounds were evaluated to have antidiabetic targets such as α-glucosidase, α-amylase, DPP-4, PPAR-γ, PTP1B and GLUT4 [24]. Hence, antidiabetic drug discovery has altered its focus to natural medicinal plant sources due to nominal side effects [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Glucose and lipid lowering effects of Enhydra fluctuans extract in cadmium treated normal and type-2 diabetic model rats

Hasan¹,

Sabrin²,

Rokeya³

et al. 2019

BMC Complement Altern Med

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BackgroundRecent epidemiological and experimental studies suggest that cadmium and diabetes-related hyperglycemia may act synergistically to worsen metabolic regulation. The present study aims to evaluate the potential effects of Enhydra fluctuans extract in diabetes and dyslipidemia in cadmium (CdCl2) induced- normal and type 2 diabetic model rats.MethodForty-eight Long-Evans rats were divided equally into the following six groups: Normal Control (N-C), Normal treated with CdCl2 (N-Cd), Normal treated with plant extract (N-P), Normal treated with both plant extract and CdCl2 (N-PCd), Diabetic treated with plant extract (DM-P) and Diabetic treated with both plant extract and CdCl2 (DM-PCd). Blood glucose and other biochemical parameters were estimated by the enzymatic colorimetric method. Histological analysis of liver and heart was done by the hematoxylin-eosin (H & E) method.ResultsTwenty-one days treatment of E. fluctuans extracts at a dose of 200 mg/kg significantly reduced blood glucose level in N-PCd and DM-PCd (p < 0.05), and DM-P (p < 0.01) group. The plant extract had no direct effects on total blood lipids but, it had beneficial effects on TG/HDL-C ratio in N-P and DM-PCd groups (p < 0.05). Cd induction significantly reduced body weight [(N-Cd, N-PCd, DM-PCd) (p < 0.01)], and induced liver [N-Cd (p < 0.05), N-PCd, p < 0.001] and renal impairment [N-Cd (p < 0.05)]. In bi-variate association, a significant positive correlation between serum glucose and SGPT (p < 0.05) as well as SGPT and TG/HDL ratio (p = 0.019) was found in DM-P and in the merged group. The histology of liver and heart showed severe damages including inflammation, nuclear pyknosis, loss of myocardial fibers, necrosis and fibrosis in the Cd treated groups compared to plant treated groups.ConclusionE. fluctuans seems to have potent antihyperglycemic effects in diabetes and Cd toxicity along with partial antidyslipidemic properties in euglycemic and diabetic rats. Our study suggests a novel oral antihyperglycemic agent in the present environmental context.

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“…High OB is normally a core indicator in the establishment of the drug likeness index of bioactive molecules (Huang et al, 2020). Drug-likeness (DL) represents the capacity of molecules in the compound demonstrating physicochemical properties comparable to existing drugs (Potunuru et al, 2019). Lipinski's Rule of Five (RO5) is an empirical guideline that predicts the high risk of poor absorption or permeability of a compound on its underlying simple physicochemical properties.…”

Section: Collection Of Bioactive Compounds and Targets Of Coix Lacryma-jobi Using Adme Evaluationmentioning

confidence: 99%

Pharmacological mechanisms on the anti-breast cancer property of Coix lacryma-jobi: A network-based analysis

Ferrer

David

Taquiqui

et al. 2021

Preprint

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Breast cancer is considered as one of the three most common cancers around the world and the second leading cause of cancer deaths among women. Coix lachrymal jobi, commonly known as Jobs tears or adlay has been reported to possess anti-cancer properties. Despite evidences provided by clinical data, the usage of Coix lacryma-jobi in treating cancer, particularly breast cancer, has been scarce. Thus, this study was conducted to determine the pharmacological mechanisms underlying its anti-breast cancer property using various network pathway analyses. Bioactive compounds from Coix lacryma-jobi and its potential target genes were obtained from SymMap. Breast cancer-related target genes were collected from CTD. Protein-protein interaction network was analyzed using the STRING database. GO and KEGG pathway enrichment analyses were performed using DAVID to further explore the mechanisms of Coix lacryma-jobi in treating breast cancer. PPI and compound-target-pathway were visualized using Cytoscape. A total of 26 bioactive compounds, 201 corresponding targets, 36625 breast cancer-associated targets were obtained, and 200 common targets were considered potential therapeutic targets. The 9 bioactive compounds identified were berberine, oleic acid, beta-sitosterol, sitosterol, linoleic acid, berberrubine, jatrorrhizine, thalifendine, and stigmasterol. The identified 5 core targets were ESR1, JUN, MAPK14, and RXRA. Coix lacryma-jobi targets enriched in GO terms were mostly involved in regulation of transcription from RNA polymerase II promoter, drug response, steroid hormone receptor activity, and protein binding. This study elucidates on the pharmacological underpinnings on the potency of adlay against breast cancer. Its subsequent drug development will be worth a step forward for a breast cancer-free society.

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Amarogentin, a secoiridoid glycoside, activates AMP- activated protein kinase (AMPK) to exert beneficial vasculo-metabolic effects

Cited by 19 publications

References 60 publications

Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress

Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress

Glucose and lipid lowering effects of Enhydra fluctuans extract in cadmium treated normal and type-2 diabetic model rats

Pharmacological mechanisms on the anti-breast cancer property of Coix lacryma-jobi: A network-based analysis

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