Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases

Han, Jung Ho; Lee, Eun-Ji; Park, Wonyoung; Ha, Ki-Tae; Chung, Hwan-Suck

doi:10.3389/fphar.2023.1275000

Cited by 13 publications

(3 citation statements)

References 353 publications

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“…Both enzymes have important metabolic roles. LDH is an enzyme of anaerobic metabolism, while MDH catalyzes one of the Krebs cycle reactions and can be considered an aerobic metabolism enzyme [38,39]. The results of our study showed a statistically significant increase in the total activities of LDH and MDH in the HPA group compared to the active control group (CPA), indicating an effect of HHcy on the total activity of these enzymes.…”

Section: Discussionmentioning

confidence: 49%

Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia

Stojanović,

Todorović,

Gopčević

et al. 2024

IJMS

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The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 μmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 μmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752–10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562–5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels.

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Section: Discussionmentioning

confidence: 49%

Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia

Stojanović,

Todorović,

Gopčević

et al. 2024

IJMS

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“…Pyruvate regulation is complex and involves key enzymes, particularly PDK and LDHA. PDK governs the entry of pyruvate into the citric acid cycle and glycolysis [96], whereas LDHA catalyzes the conversion of pyruvate to lactate under anaerobic conditions [97]. Notably, PDK and LDHA are significantly associated with EGFR-TKI resistance.…”

Section: Enhanced Glycolysis In Egfr-tki-resistant Nsclcmentioning

confidence: 99%

Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer

Park,

Han,

Wei

et al. 2024

IJMS

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Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Targeted therapy against the epidermal growth factor receptor (EGFR) is a promising treatment approach for NSCLC. However, resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major challenge in its clinical management. EGFR mutation elevates the expression of hypoxia-inducible factor-1 alpha to upregulate the production of glycolytic enzymes, increasing glycolysis and tumor resistance. The inhibition of glycolysis can be a potential strategy for overcoming EGFR-TKI resistance and enhancing the effectiveness of EGFR-TKIs. In this review, we specifically explored the effectiveness of pyruvate dehydrogenase kinase inhibitors and lactate dehydrogenase A inhibitors in combating EGFR-TKI resistance. The aim was to summarize the effects of these natural products in preclinical NSCLC models to provide a comprehensive understanding of the potential therapeutic effects. The study findings suggest that natural products can be promising inhibitors of glycolytic enzymes for the treatment of EGFR-TKI-resistant NSCLC. Further investigations through preclinical and clinical studies are required to validate the efficacy of natural product-based glycolytic inhibitors as innovative therapeutic modalities for NSCLC.

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“…Notably, key findings from current research underscore the promising role of natural products in mitigating OA symptoms, potentially influencing macrophage behavior and inflammatory responses within the joint microenvironment (7,8). Crucially, alkaloids, widespread in nature (9), play a key role in Traditional Chinese Medicine's therapeutic effects, exhibiting significant anti-cancer, anti-inflammatory, and antioxidant activities (10)(11)(12). In this context, Aconitum, commonly known as "wutou," stands out as a repository of approximately 450 alkaloids and has been extensively utilized for treating various diseases in China, Japan, and other regions (13, 14).…”

Section: Introductionmentioning

confidence: 99%

Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis

He,

Huang,

et al. 2024

Front. Immunol.

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IntroductionOsteoarthritis (OA) is a prevalent joint disorder characterized by multifaceted pathogenesis, with macrophage dysregulation playing a critical role in perpetuating inflammation and joint degeneration. MethodsThis study focuses on Songorine, derived from Aconitum soongaricum Stapf, aiming to unravel its therapeutic mechanisms in OA. Comprehensive analyses, including PCR, Western blot, and immunofluorescence, were employed to evaluate Songorine's impact on the joint microenvironment and macrophage polarization. RNA-seq analysis was conducted to unravel its anti-inflammatory mechanisms in macrophages. Metabolic alterations were explored through extracellular acidification rate monitoring, molecular docking simulations, and PCR assays. Oxygen consumption rate measurements were used to assess mitochondrial oxidative phosphorylation, and Songorine's influence on macrophage oxidative stress was evaluated through gene expression and ROS assays.ResultsSongorine effectively shifted macrophage polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Notably, Songorine induced metabolic reprogramming, inhibiting glycolysis and promoting mitochondrial oxidative phosphorylation. This metabolic shift correlated with a reduction in macrophage oxidative stress, highlighting Songorine's potential as an oxidative stress inhibitor.DiscussionIn an in vivo rat model of OA, Songorine exhibited protective effects against cartilage damage and synovial inflammation, emphasizing its therapeutic potential. This comprehensive study elucidates Songorine's multifaceted impact on macrophage modulation, metabolic reprogramming, and the inflammatory microenvironment, providing a theoretical foundation for its therapeutic potential in OA.

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Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases

Cited by 13 publications

References 353 publications

Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia

Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia

Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer

Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis

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