The Changes in Endogenous Metabolites in Hyperlipidemic Rats Treated with Herbal Mixture Containing Lemon, Apple Cider, Garlic, Ginger, and Honey

An herbal mixture composed of lemon, apple cider, garlic, ginger and honey as a polyphenol-rich mixture (PRM) has been reported to contain hypolipidemic activity on human subjects and hyperlipidemic rats. However, the therapeutic effects of PRM on metabolites are not clearly understood. Therefore, this study aimed to provide new information on the causal impact of PRM on the endogenous metabolites, pathways and serum biochemistry. Serum samples of hyperlipidemic rats treated with PRM were subjected to biochemistry (lipid and liver profile) and hydroxymethylglutaryl-CoA enzyme reductase (HMG-CoA reductase) analyses. In contrast, the urine samples were subjected to urine metabolomics using 1H NMR. The serum biochemistry revealed that PRM at 500 mg/kg (PRM-H) managed to lower the total cholesterol level and low-density lipoprotein (LDL-C) (p < 0.05) and reduce the HMG-CoA reductase activity. The pathway analysis from urine metabolomics reveals that PRM-H altered 17 pathways, with the TCA cycle having the highest impact (0.26). Results also showed the relationship between the serum biochemistry of LDL-C and HMG-CoA reductase and urine metabolites (trimethylamine-N-oxide, dimethylglycine, allantoin and succinate). The study’s findings demonstrated the potential of PRM at 500 mg/kg as an anti-hyperlipidemic by altering the TCA cycle, inhibiting HMG-CoA reductase and lowering the LDL-C in high cholesterol rats.

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Glycation and HMG-CoA Reductase Inhibitors: Implication in Diabetes and Associated Complications

Current Diabetes Reviews ◽

10.2174/1573399814666180924113442 ◽

2019 ◽

Vol 15 (3) ◽

pp. 213-223 ◽

Cited By ~ 3

Author(s):

Rabia Nabi ◽

Sahir Sultan Alvi ◽

Mohd. Saeed ◽

Saheem Ahmad ◽

Mohammad Salman Khan

Keyword(s):

Oxidized Ldl ◽

Advanced Glycation Endproducts ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Protective Role ◽

Therapeutic Effects ◽

Hmg Coa Reductase ◽

Toxicological Effects ◽

Coa Reductase

Introduction: Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk, prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced Advanced Glycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhanced glyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicity and decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG) prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusual pharmaco-toxicological effects thus restraining its desirable therapeutic effects. HMG-R inhibitors/statins exhibit a variety of beneficial impacts in addition to the cholesterol-lowering effects. Objective: Inhibition of AGEs interaction with receptor for AGEs (RAGE) and glyco-oxidized-LDL by HMG-R inhibitors could decrease LDL uptake by LDL-receptor (LDL-R), regulate cholesterol synthesis via HMG-R, decrease oxidative and inflammatory stress to improve the diabetes-associated complications. Conclusion: Current article appraises the pathological AGE-RAGE concerns in diabetes and its associated complications, mainly focusing on the phenomenon of both circulatory AGEs and those accumulating in tissues in diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy, discussing the potential protective role of HMG-R inhibitors against diabetic complications.

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Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabolomics for Discovering Potential Biomarkers and Metabolic Pathways of Colorectal Cancer in Mouse Model (ApcMin/+) and Revealing the Effect of Honokiol

Frontiers in Oncology ◽

10.3389/fonc.2021.671014 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xin Chen ◽

Bo-lun Shi ◽

Run-zhi Qi ◽

Xing Chang ◽

Hong-gang Zheng

Keyword(s):

Colorectal Cancer ◽

Mouse Model ◽

Metabolic Pathways ◽

Molecular Mechanisms ◽

Tca Cycle ◽

Ultra Performance Liquid Chromatography ◽

Therapeutic Effects ◽

Anticancer Activities ◽

Metabolic Disturbances ◽

Endogenous Metabolites

Endogenous metabolites are a class of molecules playing diverse and significant roles in many metabolic pathways for disease. Honokiol (HNK), an active poly-phenolic compound, has shown potent anticancer activities. However, the detailed crucial mechanism regulated by HNK in colorectal cancer remains unclear. In the present study, we investigated the therapeutic effects and the underlying molecular mechanisms of HNK on colorectal cancer in a mouse model (ApcMin/+) by analyzing the urine metabolic profile based on metabolomics, which is a powerful tool for characterizing metabolic disturbances. We found that potential urine biomarkers were involved in the metabolism of compounds such as purines, tyrosines, tryptophans, etc. Moreover, we showed that a total of 27 metabolites were the most contribution biomarkers for intestinal tumors, and we found that the citrate cycle (TCA cycle) was regulated by HNK. In addition, it was suggested that the efficacy of HNK was achieved by affecting the multi-pathway system via influencing relevant metabolic pathways and regulating metabolic function. Our work also showed that high-throughput metabolomics can characterize the regulation of metabolic disorders as a therapeutic strategy to prevent colorectal cancer.

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Contribution of Vascular NAD(P)H Oxidase to Endothelial Dysfunction in Heart Failure and the Therapeutic Effects of HMG-CoA Reductase Inhibitor

Circulation Journal ◽

10.1253/circj.68.1067 ◽

2004 ◽

Vol 68 (11) ◽

pp. 1067-1075 ◽

Cited By ~ 24

Author(s):

Tomoyuki Takayama ◽

Atsuyuki Wada ◽

Takayoshi Tsutamoto ◽

Masato Ohnishi ◽

Masanori Fujii ◽

...

Keyword(s):

Heart Failure ◽

Endothelial Dysfunction ◽

Reductase Inhibitor ◽

Therapeutic Effects ◽

Hmg Coa Reductase ◽

Hmg Coa Reductase Inhibitor ◽

Coa Reductase

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Metabonomic approaches investigate diosbulbin B-induced pulmonary toxicity and elucidate its underling mechanism in male mice

Toxicology Research ◽

10.1093/toxres/tfab014 ◽

2021 ◽

Vol 10 (2) ◽

pp. 272-276

Author(s):

Hainan Ji ◽

Chang Liu ◽

Na Tong ◽

Naining Song ◽

Baoliang Xu ◽

...

Keyword(s):

Molecular Mechanism ◽

Tca Cycle ◽

Lung Toxicity ◽

Mouse Lung ◽

Lung Cells ◽

Dependent Manner ◽

The Tca Cycle ◽

Atp Supply ◽

Endogenous Metabolites ◽

Dose Dependent

Abstract Air Potato Yam is widely used in the treatment of many conditions such as cancer, inflammation, and goiter. Diosbulbin B (DIOB) is the primary active component of Air Potato Yam, and it exhibits anti-tumor and anti-inflammatory properties. The main purpose of this study was to determine the mechanism by which DIOB induces lung toxicity, using metabonomics and molecular biology techniques. The results showed that the lung toxicity induced by DIOB may occur because of a DIOB-induced increase in the plasma levels of long-chain free fatty acids and endogenous metabolites related to inflammation. In addition, treatment with DIOB increases the expression of the cyp3a13 enzyme, which leads to enhanced toxicity in a dose-dependent manner. The molecular mechanism underlying toxicity in mouse lung cells is the DIOB-mediated inhibition of fatty acid β-oxidation, partial glycolysis, and the TCA cycle, but DIOB treatment can also compensate for the low Adenosine triphosphate (ATP) supply levels by improving the efficiency of the last step of the glycolysis reaction and by increasing the rate of anaerobic glycolysis. Using metabonomics and other methods, we identified the toxic effects of DIOB on the lung and clarified the underlying molecular mechanism.

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Enhanced 3-Hydroxypropionic Acid Production From Acetate via the Malonyl-CoA Pathway in Corynebacterium glutamicum

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.808258 ◽

2022 ◽

Vol 9 ◽

Author(s):

Zhishuai Chang ◽

Wei Dai ◽

Yufeng Mao ◽

Zhenzhen Cui ◽

Zhidan Zhang ◽

...

Keyword(s):

Corynebacterium Glutamicum ◽

Citrate Synthase ◽

Tca Cycle ◽

Acid Synthesis ◽

Acetyl Coa ◽

The Tca Cycle ◽

Malonyl Coa ◽

Alternative Carbon Source ◽

Coa Reductase ◽

Hydroxypropionic Acid

Acetate is an economical and environmental-friendly alternative carbon source. Herein, the potential of harnessing Corynebacterium glutamicum as a host to produce 3-hydroxypropionic acid (3-HP) from acetate was explored. First, the expression level of malonyl-CoA reductase from Chloroflexus aurantiacus was optimized through several strategies, strain Cgz2/sod-N-C* showed an MCR enzyme activity of 63 nmol/mg/min and a 3-HP titer of 0.66 g/L in flasks. Next, the expression of citrate synthase in Cgz2/sod-N-C* was weakened to reduce the acetyl-CoA consumption in the TCA cycle, and the resulting strain Cgz12/sod-N-C* produced 2.39 g/L 3-HP from 9.32 g/L acetate. However, the subsequent deregulation of the expression of acetyl-CoA carboxylase genes in Cgz12/sod-N-C* resulted in an increased accumulation of intracellular fatty acids, instead of 3-HP. Accordingly, cerulenin was used to inhibit fatty acid synthesis in Cgz14/sod-N-C*, and its 3-HP titer was further increased to 4.26 g/L, with a yield of 0.50 g 3-HP/g-acetate. Finally, the engineered strain accumulated 17.1 g/L 3-HP in a bioreactor without cerulenin addition, representing the highest titer achieved using acetate as substrate. The results demonstrated that Corynebacterium glutamicum is a promising host for 3-HP production from acetate.

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