Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments.

Natural compounds such as curcumin, a polyphenolic compound derived from the rhizome of turmeric, have gathered remarkable scientific interest due to their diverse metabolic benefits including anti-obesity potential. However, curcumin faces challenges stemming from its unfavorable pharmacokinetic profile. To address this issue, synthetic curcumin derivatives aimed at enhancing the biological efficacy of curcumin have previously been developed. In silico modelling techniques have gained significant recognition in screening synthetic compounds as drug candidates. Therefore, the primary objective of this study was to assess the pharmacokinetic and pharmacodynamic characteristics of three synthetic derivatives of curcumin. This evaluation was conducted in comparison to curcumin, with a specific emphasis on examining their impact on adipogenesis, inflammation, and lipid metabolism as potential therapeutic targets of obesity mechanisms. In this study, predictive toxicity screening confirmed the safety of curcumin, with the curcumin derivatives demonstrating a safe profile based on their LD50 values. The synthetic curcumin derivative 1A8 exhibited inactivity across all selected toxicity endpoints. Furthermore, these compounds were deemed viable candidate drugs as they adhered to Lipinski's rules and exhibited favorable metabolic profiles. Molecular docking studies revealed that both curcumin and its synthetic derivatives exhibited favorable binding scores, whilst molecular dynamic simulations showed stable binding with peroxisome proliferator-activated receptor gamma (PPARγ), csyclooxygenase-2 (COX2), and fatty acid synthase (FAS) proteins. The binding free energy calculations indicated that curcumin displayed potential as a strong regulator of PPARγ (-60.2 ± 0.4 kcal/mol) and FAS (-37.9 ± 0.3 kcal/mol), whereas 1A8 demonstrated robust binding affinity with COX2 (-64.9 ± 0.2 kcal/mol). In conclusion, the results from this study suggest that the three synthetic curcumin derivatives have similar molecular interactions to curcumin with selected biological targets. However, in vitro and in vivo experimental studies are recommended to validate these findings.

Low levels and partial exposure to palmitic acid improves mitochondrial function and the oxidative status of cultured cardiomyoblasts.

Lipid overload or metabolic stress has gained popularity in research that explores pathological mechanisms that may drive enhanced oxidative myocardial damage. Here, H9c2 cardiomyoblasts were exposed to various doses of palmitic acid (0.06 to 1 mM) for either 4 or 24 h to study its potential physiological response to cardiac cells. Briefly, assays performed included metabolic activity, cholesterol content, mitochondrial respiration, and prominent markers of oxidative stress, as well as determining changes in mitochondrial potential, mitochondrial production of reactive oxygen species, and intracellular antioxidant levels like glutathione, glutathione peroxidase and superoxide dismutase. Cellular damage was probed using fluorescent stains, annexin V and propidium iodide. Our results indicated that prolonged exposure (24-hours) to palmitic acid doses ≥ 0.5 mM significantly impaired mitochondrial oxidative status, leading to enhanced mitochondrial membrane potential and increased mitochondrial ROS production. While palmitic acid dose of 1 mM appeared to induce prominent cardiomyoblasts damage, likely because of its capacity to increase cholesterol content/ lipid peroxidation and severely suppressing intracellular antioxidants. Interestingly, short-term (4-hours) exposure to palmitic acid, especially for lower doses (≤ 0.25 mM), could improve metabolic activity, mitochondrial function and protect against oxidative stress induced myocardial damage. Potentially suggesting that, depending on the dose consumed or duration of exposure, consumption of saturated fatty acids such as palmitic acid can differently affect the myocardium. However, these results are still preliminary, and in vivo research is required to understand the significance of maintaining intracellular antioxidants to protect against oxidative stress induced by lipid overload.

Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.

High-fat diet (HFD) feeding in rodents has become an essential tool to critically analyze and study the pathological effects of obesity, including mitochondrial dysfunction and insulin resistance. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates cellular energy metabolism to influence insulin sensitivity, beyond its active role in stimulating mitochondrial biogenesis to facilitate skeletal muscle adaptations in response to HFD feeding. Here, some of the major electronic databases like PubMed, Embase, and Web of Science were accessed to update and critically discuss information on the potential role of PGC-1α during metabolic adaptations within the skeletal muscle in response to HFD feeding in rodents. In fact, available evidence suggests that partial exposure to HFD feeding (potentially during the early stages of disease development) is associated with impaired metabolic adaptations within the skeletal muscle, including mitochondrial dysfunction and reduced insulin sensitivity. In terms of implicated molecular mechanisms, these negative effects are partially associated with reduced activity of PGC-1α, together with the phosphorylation of protein kinase B and altered expression of genes involving nuclear respiratory factor 1 and mitochondrial transcription factor A within the skeletal muscle. Notably, metabolic abnormalities observed with chronic exposure to HFD (likely during the late stages of disease development) may potentially occur independently of PGC-1α regulation within the muscle of rodents. Summarized evidence suggests the causal relationship between PGC-1α regulation and effective modulations of mitochondrial biogenesis and metabolic flexibility during the different stages of disease development. It further indicates that prominent interventions like caloric restriction and physical exercise may affect PGC-1α regulation during effective modulation of metabolic processes.

Brown adipose tissue-derived metabolites and their role in regulating metabolism.

The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as "batokines", which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.

Sulforaphane: A nutraceutical against diabetes-related complications.

There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.

Potential Benefits of Coffee Consumption on Improving Biomarkers of Oxidative Stress and Inflammation in Healthy Individuals and Those at Increased Risk of Cardiovascular Disease.

Cardiovascular diseases (CVDs) are considered the predominant cause of death globally. An abnormal increase in biomarkers of oxidative stress and inflammation are consistently linked with the development and even progression of metabolic diseases, including enhanced CVD risk. Coffee is considered one of the most consumed beverages in the world, while reviewed evidence regarding its capacity to modulate biomarkers of oxidative stress and inflammation remains limited. The current study made use of prominent electronic databases, including PubMed, Google Scholar, and Scopus to retrieve information from randomized controlled trials reporting on any association between coffee consumption and modulation of biomarkers of oxidative stress and inflammation in healthy individuals or those at increased risk of developing CVD. In fact, summarized evidence indicates that coffee consumption, mainly due to its abundant antioxidant properties, can reduce biomarkers of oxidative stress and inflammation, which can be essential in alleviating the CVD risk in healthy individuals. However, more evidence suggests that regular/prolonged use or long term (>4 weeks) consumption of coffee appeared to be more beneficial in comparison with short-term intake (<4 weeks). These positive effects are also observed in individuals already presenting with increased CVD risk, although such evidence is very limited. The current analysis of data highlights the importance of understanding how coffee consumption can be beneficial in strengthening intracellular antioxidants to alleviate pathological features of oxidative stress and inflammation to reduce CVD risk within the general population. Also covered within the review is essential information on the metabolism and bioavailability profile of coffee, especially caffeine as one of its major bioactive compounds.

Bioactive Properties, Bioavailability Profiles, and Clinical Evidence of the Potential Benefits of Black Pepper (Piper nigrum) and Red Pepper (Capsicum annum) against Diverse Metabolic Complications.

The consumption of food-derived products, including the regular intake of pepper, is increasingly evaluated for its potential benefits in protecting against diverse metabolic complications. The current study made use of prominent electronic databases including PubMed, Google Scholar, and Scopus to retrieve clinical evidence linking the intake of black and red pepper with the amelioration of metabolic complications. The findings summarize evidence supporting the beneficial effects of black pepper (Piper nigrum L.), including its active ingredient, piperine, in improving blood lipid profiles, including reducing circulating levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in overweight and obese individuals. The intake of piperine was also linked with enhanced antioxidant and anti-inflammatory properties by increasing serum levels of superoxide dismutase while reducing those of malonaldehyde and C-reactive protein in individuals with metabolic syndrome. Evidence summarized in the current review also indicates that red pepper (Capsicum annum), together with its active ingredient, capsaicin, could promote energy expenditure, including limiting energy intake, which is likely to contribute to reduced fat mass in overweight and obese individuals. Emerging clinical evidence also indicates that pepper may be beneficial in alleviating complications linked with other chronic conditions, including osteoarthritis, oropharyngeal dysphagia, digestion, hemodialysis, and neuromuscular fatigue. Notably, the beneficial effects of pepper or its active ingredients appear to be more pronounced when used in combination with other bioactive compounds. The current review also covers essential information on the metabolism and bioavailability profiles of both pepper species and their main active ingredients, which are all necessary to understand their potential beneficial effects against metabolic diseases.

Therapeutic Effects of Curcumin Derivatives against Obesity and Associated Metabolic Complications: A Review of In Vitro and In Vivo Studies.

Obesity is a major cause of morbidity and mortality globally, increasing the risk for chronic diseases. Thus, the need to identify more effective anti-obesity agents has spurred significant interest in the health-promoting properties of natural compounds. Of these, curcumin, the most abundant and bioactive constituent of turmeric, possesses a variety of health benefits including anti-obesity effects. However, despite its anti-obesity potential, curcumin has demonstrated poor bioavailability, which limits its clinical applicability. Synthesizing curcumin derivatives, which are structurally modified analogs of curcumin, has been postulated to improve bioavailability while maintaining therapeutic efficacy. This review summarizes in vitro and in vivo studies that assessed the effects of curcumin derivatives against obesity and its associated metabolic complications. We identified eight synthetic curcumin derivatives that were shown to ameliorate obesity and metabolic dysfunction in diet-induced obese animal models, while five of these derivatives also attenuated obesity and associated metabolic complications in cell culture models. These curcumin derivatives modulated adipogenesis, lipid metabolism, insulin resistance, steatosis, lipotoxicity, inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, fibrosis, and dyslipidemia to a greater extent than curcumin. In conclusion, the findings from this review show that compared to curcumin, synthetic curcumin derivatives present potential candidates for further development as therapeutic agents to modulate obesity and obesity-associated metabolic complications.

Sarcopenia in a type 2 diabetic state: Reviewing literature on the pathological consequences of oxidative stress and inflammation beyond the neutralizing effect of intracellular antioxidants.

Sarcopenia remains one of the major pathological features of type 2 diabetes (T2D), especially in older individuals. This condition describes gradual loss of muscle mass, strength, and function that reduces the overall vitality and fitness, leading to increased hospitalizations and even fatalities to those affected. Preclinical evidence indicates that dysregulated mitochondrial dynamics, together with impaired activity of the NADPH oxidase system, are the major sources of oxidative stress that drive skeletal muscle damage in T2D. While patients with T2D also display relatively higher levels of circulating inflammatory markers in the serum, including high sensitivity-C-reactive protein, interleukin-6, and tumor necrosis factor-α that are independently linked with the deterioration of muscle function and sarcopenia in T2D. In fact, beyond reporting on the pathological consequences of both oxidative stress and inflammation, the current review highlights the importance of strengthening intracellular antioxidant systems to preserve muscle mass, strength, and function in individuals with T2D.

Dietary supplementation of low levels of unprocessed Mucuna pruriens utilis seed meal induces mild antinutritional entero-physio-metabolic perturbations without compromising performance and meat quality in finisher broilers.

The rapidly growing world human population accentuates the need for improved production especially of protein-rich food. Broiler meat production offers opportunity to ensure security of this food. However, the production of modern broilers is not only limited by high feed costs due to dietary use of expensive energy and protein sources but also their meat possesses undesirable quality attributes. This study thus examined the effect of dietary Mucuna pruriens utilis seed meal (MSM) on growth performance, blood profile, carcass traits, and meat quality in finisher broiler chickens. In a completely randomised design (CRD), 320 21-day-old chicks were randomly allocated to 32 pens in which they were allotted 4 dietary treatments with 0, 2.5, 5, and 10% MSM, each with 8 replicate pens of 10 birds, for 28 days. Growth performance, carcass characteristics, internal organs, haemato-biochemistry, and meat quality were measured. Results showed that dietary MSM did not affect (P > 0.05) broiler performance, weights, and lengths of carcass cuts and internal organs, haematology, and meat quality. The only exception was MSM-induced increase in duodenal weight (linear, P < 0.05) and serum phosphorus (quadratic, P = 0.05) in contrast to a decrease in procalcitonin (quadratic, P < 0.01) and serum levels of total protein (linear, P < 0.05; and quadratic, P < 0.01), albumin (quadratic, P < 0.05), and bilirubin (quadratic, P = 0.001). Therefore, MSM could be supplemented up to 10% without compromising performance, carcass traits, internal organs, haemato-biochemistry, and meat quality in finisher broiler diets.

Pathological Role of Oxidative Stress in Aflatoxin-Induced Toxicity in Different Experimental Models and Protective Effect of Phytochemicals: A Review.

Aflatoxin B1 is a secondary metabolite with a potentially devastating effect in causing liver damage in broiler chickens, and this is mainly facilitated through the generation of oxidative stress and malonaldehyde build-up. In the past few years, significant progress has been made in controlling the invasion of aflatoxins. Phytochemicals are some of the commonly used molecules endowed with potential therapeutic effects to ameliorate aflatoxin, by inhibiting the production of reactive oxygen species and enhancing intracellular antioxidant enzymes. Experimental models involving cell cultures and broiler chickens exposed to aflatoxin or contaminated diet have been used to investigate the ameliorative effects of phytochemicals against aflatoxin toxicity. Electronic databases such as PubMed, Science Direct, and Google Scholar were used to identify relevant data sources. The retrieved information reported on the link between aflatoxin B1-included cytotoxicity and the ameliorative potential/role of phytochemicals in chickens. Importantly, retrieved data showed that phytochemicals may potentially protect against aflatoxin B1-induced cytotoxicity by ameliorating oxidative stress and enhancing intracellular antioxidants. Preclinical data indicate that activation of nuclear factor erythroid 2-related factor 2 (Nrf2), together with its downstream antioxidant genes, may be a potential therapeutic mechanism by which phytochemicals neutralize oxidative stress. This highlights the need for more research to determine whether phytochemicals can be considered a useful therapeutic intervention in controlling mycotoxins to improve broiler health and productivity.

Pancreatic ß-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress.

Insulin resistance and pancreatic ß-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes (T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define ß-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1ß are consistently associated with ß-cell failure in preclinical models and in people with T2D. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic ß-cell damage in conditions of T2D. Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D. The current review explores preclinical and clinical research on the patho-logical implications of inflammation and oxidative stress during the development of ß-cell dysfunction in T2D. Moreover, important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress during ß-cell failure in T2D. Underpinning the clinical relevance of the review, a systematic analysis of evidence from randomized controlled trials is covered, on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improve ß-cell function.

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin.

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as a potential avenue to combat obesity. Although BAT is the opposite of white adipose tissue (WAT) which is responsible for energy storage, BAT shares thermogenic capacity with beige adipose tissue that emerges from WAT depots. This is unsurprising as both BAT and beige adipose tissue display a huge difference from WAT in terms of their secretory profile and physiological role. In obesity, the content of BAT and beige adipose tissue declines as these tissues acquire the WAT characteristics via the process called "whitening". This process has been rarely explored for its implication in obesity, whether it contributes to or exacerbates obesity. Emerging research has demonstrated that BAT/beige adipose tissue whitening is a sophisticated metabolic complication of obesity that is linked to multiple factors. The current review provides clarification on the influence of various factors such as diet, age, genetics, thermoneutrality, and chemical exposure on BAT/beige adipose tissue whitening. Moreover, the defects and mechanisms that underpin the whitening are described. Notably, the BAT/beige adipose tissue whitening can be marked by the accumulation of large unilocular lipid droplets, mitochondrial degeneration, and collapsed thermogenic capacity, by the virtue of mitochondrial dysfunction, devascularization, autophagy, and inflammation.

Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials.

Cardiovascular diseases (CVDs) continue to be the leading cause of death in people with diabetes mellitus. Severely suppressed intracellular antioxidant defenses, including low plasma glutathione (GSH) levels, are consistently linked with the pathological features of diabetes such as oxidative stress and inflammation. In fact, it has already been established that low plasma GSH levels are associated with increased risk of CVD in people with diabetes. Dietary supplements are widely used and may offer therapeutic benefits for people with diabetes at an increased risk of developing CVDs. However, such information remains to be thoroughly scrutinized. Hence, the current systematic review explored prominent search engines, including PubMed and Google Scholar, for updated literature from randomized clinical trials reporting on the effects of dietary supplements on plasma GSH levels in people with diabetes. Available evidence indicates that dietary supplements, such as coenzyme Q10, selenium, curcumin, omega-3 fatty acids, and vitamin E or D, may potentially improve cardiometabolic health in patients with diabetes. Such beneficial effects are related to enhancing plasma GSH levels and reducing cholesterol, including biomarkers of oxidative stress and inflammation. However, available evidence is very limited and additional clinical studies are still required to validate these findings, including resolving issues related to the bioavailability of these bioactive compounds.

Anti-Obesity Effects of Metformin: A Scoping Review Evaluating the Feasibility of Brown Adipose Tissue as a Therapeutic Target.

Brown adipose tissue (BAT) is increasingly recognized as the major therapeutic target to promote energy expenditure and ameliorate diverse metabolic complications. There is a general interest in understanding the pleiotropic effects of metformin against metabolic complications. Major electronic databases and search engines such as PubMed/MEDLINE, Google Scholar, and the Cochrane library were used to retrieve and critically discuss evidence reporting on the impact of metformin on regulating BAT thermogenic activity to ameliorate complications linked with obesity. The summarized evidence suggests that metformin can reduce body weight, enhance insulin sensitivity, and improve glucose metabolism by promoting BAT thermogenic activity in preclinical models of obesity. Notably, this anti-diabetic agent can affect the expression of major thermogenic transcriptional factors such as uncoupling protein 1 (UCP1), nuclear respiratory factor 1 (NRF1), and peroxisome-proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) to improve BAT mitochondrial function and promote energy expenditure. Interestingly, vital molecular markers involved in glucose metabolism and energy regulation such as AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21) are similarly upregulated by metformin treatment in preclinical models of obesity. The current review also discusses the clinical relevance of BAT and thermogenesis as therapeutic targets. This review explored critical components including effective dosage and appropriate intervention period, consistent with the beneficial effects of metformin against obesity-associated complications.

Corrigendum: A review on the antidiabetic properties of Moringa oleifera extracts: Focusing on oxidative stress and inflammation as main therapeutic targets.

[This corrects the article DOI: 10.3389/fphar.2022.940572.].

Disease progression promotes changes in adipose tissue signatures in type 2 diabetic (db/db) mice: The potential pathophysiological role of batokines.

Unlike the white adipose tissue (WAT) which mainly stores excess energy as fat, brown adipose tissue (BAT) has become physiologically important and therapeutically relevant for its prominent role in regulating energy metabolism. The current study makes use of an established animal model of type 2 diabetes (T2D) db/db mice to determine the effect of the disease progression on adipose tissue morphology and gene regulatory signatures. Results showed that WAT and BAT from db/db mice display a hypertrophied phenotype that is consistent with increased expression of the pro-inflammatory cytokine, tumor necrosis factor-alpha (Tnf-α). Moreover, BAT from both db/db and non-diabetic db/+ control mice displayed an age-related impairment in glucose homeostasis, inflammatory profile, and thermogenic regulation, as demonstrated by reduced expression of genes like glucose transporter (Glut-4), adiponectin (AdipoQ), and uncoupling protein 1 (Ucp-1). Importantly, gene expression of the batokines regulating sympathetic neurite outgrowth and vascularization, including bone morphogenic protein 8b (Bmp8b), fibroblast growth factor 21 (Fgf-21), neuregulin 4 (Nrg-4) were altered in BAT from db/db mice. Likewise, gene expression of meteorin-like (Metrnl), growth differentiation factor 15 (Gdt-15), and C-X-C motif chemokine-14 (Cxcl-14) regulating pro- and anti-inflammation were altered. This data provides some new insights into the pathophysiological mechanisms involved in BAT hypertrophy (or whitening) and the disturbances of batokines during the development and progression of T2D. However, these are only preliminary results as additional experiments are necessary to confirm these findings in other experimental models of T2D.

Impact of dyslipidemia in the development of cardiovascular complications: Delineating the potential therapeutic role of coenzyme Q10.

Dyslipidemia is one of the major risk factors for the development of cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). This metabolic anomality is implicated in the generation of oxidative stress, an inevitable process involved in destructive mechanisms leading to myocardial damage. Fortunately, commonly used drugs like statins can counteract the detrimental effects of dyslipidemia by lowering cholesterol to reduce CVD-risk in patients with T2D. Statins mainly function by blocking the production of cholesterol by targeting the mevalonate pathway. However, by blocking cholesterol synthesis, statins coincidently inhibit the synthesis of other essential isoprenoid intermediates of the mevalonate pathway like farnesyl pyrophosphate and coenzyme Q10 (CoQ10). The latter is by far the most important co-factor and co-enzyme required for efficient mitochondrial oxidative capacity, in addition to its robust antioxidant properties. In fact, supplementation with CoQ10 has been found to be beneficial in ameliorating oxidative stress and improving blood flow in subjects with mild dyslipidemia.. Beyond discussing the destructive effects of oxidative stress in dyslipidemia-induced CVD-related complications, the current review brings a unique perspective in exploring the mevalonate pathway to block cholesterol synthesis while enhancing or maintaining CoQ10 levels in conditions of dyslipidemia. Furthermore, this review disscusses the therapeutic potential of bioactive compounds in targeting the downstream of the mevalonate pathway, more importantly, their ability to block cholesterol while maintaining CoQ10 biosynthesis to protect against the destructive complications of dyslipidemia.

Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials.

Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Conclusion: Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD.

Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants.

Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q10, glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E.