M3, a 1,4-Dihydropyridine Derivative and Mixed L-/T-Type Calcium Channel Blocker, Attenuates Isoproterenol-Induced Toxicity in Male Wistar Rats

Kale, Oluwafemi Ezekiel; Gündüz, Miyase Gözde; Ogunbiyi, Babafemi Tosin; Ogundare, Temitope Funmi; Ekor, Martins; Awodele, Olufunsho

doi:10.1007/s12012-020-09587-1

Cited by 3 publications

(2 citation statements)

References 49 publications

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“…Evidence is accumulating that calcium channel blockers exert hepatoprotective function by preventing oxidative stress (Kale et al, 2020; Yao et al, 2020). We thus detected the SOD activity in liver and found that there is no difference in SOD activity among groups (Figure 3d).…”

Section: Resultsmentioning

confidence: 99%

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Yang

Zhao

Qian

et al. 2022

British J Pharmacology

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Background and Purpose Non‐alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s. Experimental Approach Mice were fed with high‐fat diet (HFD) and 0.05% N‐nitro‐L‐arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum. Key Results Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate‐ and amlodipine aspartate‐treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD‐fed hypertensive mice. Conclusion and Implications Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.

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Section: Resultsmentioning

confidence: 99%

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Yang

Zhao

Qian

et al. 2022

British J Pharmacology

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“…1,4-dihydropyridines are N-heterocycles belonging to a broad class of polyhydroquinoline derivatives that showed excessive biological activities which include anticancer [18,19] antibacterial, [20] antiinflammatory, [21] selective acetylcholinesterase inhibitors [22] cardiovascular, [8] myorelaxant, [23] and analgesic. [8] In addition, these compounds are also important building blocks for polymer synthesis, [24] fluorescent probechemo sensors, [25] notch inhibitors, [26] calcium channel antagonist, [1,[27][28][29] bone anabolic agent, [30] and active against TGFβ mediated/SMAD signalling. [31,32] Polyhydroquinolines con-tain a fused heterocyclic entity having dihydropyridine (DHP) and a cyclohexanone ring.…”

Section: Introductionmentioning

confidence: 99%

Application of Cyclohexane‐1,3‐diones in the Synthesis of Six‐Membered Nitrogen‐Containing Heterocycles

Sharma¹,

Kumar

et al. 2022

ChemistrySelect

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Cyclohexane‐1,3‐dione and its derivatives are imperative precursors in synthetic organic chemistry as they are useful intermediates for the synthesis of a wide range of biologically active natural products, heterocycles and pharmaceuticals. Recently, cyclohexane‐1,3‐diones have been used for the synthesis of varied array of six‐membered nitrogen‐containing heterocycles in the presence of aldehydes, acetoacetic esters, malononitrile, chalcones, coumarins, acetophenones, amino acids, amines, etc. under catalytic and non‐catalytic conditions. Newest studies on the importance of these heterocycles motivated us to compile all the recently developed processes which include the fabrication of six‐membered nitrogen heterocycles. This article is mainly focused on the efficient synthesis of six‐membered N‐heterocycles i. e. 1,4‐dihydropyridine, acridine‐1,8‐diones, benzoacridinones, quinolones and pyridine derivatives from cyclohexane‐1,3‐diones as one of the substrates, published for the last ten years.

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β-Enaminones from cyclohexane-1,3-diones: Versatile precursors for nitrogen and oxygen-containing heterocycles synthesis

Sharma¹,

Kumar²,

Kumar

et al. 2023

Synthetic Communications

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M3, a 1,4-Dihydropyridine Derivative and Mixed L-/T-Type Calcium Channel Blocker, Attenuates Isoproterenol-Induced Toxicity in Male Wistar Rats

Cited by 3 publications

References 49 publications

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Application of Cyclohexane‐1,3‐diones in the Synthesis of Six‐Membered Nitrogen‐Containing Heterocycles

β-Enaminones from cyclohexane-1,3-diones: Versatile precursors for nitrogen and oxygen-containing heterocycles synthesis

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