Although adipose tissue controls metabolism and protects vital organs, its importance to general health is being highlighted by the rise in type 2 diabetes and cardiovascular disease. Adipokines produced by adipose cells are essential regulators of metabolism, glucose homeostasis, and inflammatory response. It also protects vascular endothelial cells for its potential implications for cardiovascular protection. Understanding its intricate involvement in adipose tissue-endothelial communication is critical in developing targeted therapeutics to treat cardiovascular conditions linked with obesity and metabolic dysregulation. Spices from the Zingiberaceae family, such as cardamom, turmeric, and ginger, have anti-inflammatory and anti-oxidant properties that help reduce oxidative stress, vascular dysfunction, and adipocyte-endothelial crosstalk which are all linked to the etiology of CVD. Comprehensive molecular insights into how they modulate adipokine signalling, inflammatory pathways, and ROS-induced adipocyte-vascular interactions remain unexplored, demanding additional translational and clinical validation. With an emphasis on patients with obesity and metabolic dysregulation, the investigation aims to elucidate the mechanisms by which the spice as whole/bioactive constituents of the Zingiberaceae family may provide protection against CVD by integrating previous studies.

Current research continues to support the use of spices from the Zingiberaceae family, such as ginger, turmeric, cardamom, and pepper, as potential therapeutic agents for addressing metabolic complications like obesity, type II diabetes, and CVDs. These natural remedies may modulate adipocyte-endothelial crosstalk and inflammation by modulating important signalling pathways such as AMPK, AKT, PPAR, and NF-κB..

This review provides a complete summary of existing knowledge, opening the way for future research and prospective therapeutic applications of Zingiberaceae spices in cardiovascular health management.

Curcumin, a polyphenolic compound derived from Curcuma longa, has gained significant attention for its potential therapeutic benefits, particularly counteracting inflammation, oxidative stress, and metabolic disorders. Its chemical structure, featuring conjugated double bonds between two aromatic rings, allows it to act as an electron donor, thereby mitigating free radical formation. Despite its poor solubility in water, curcumin is stable in acidic environments and undergoes significant metabolism in both the liver and the gut. Intestinal microbiota, particularly at the colon level, further metabolizes curcumin into several derivatives, including dihydrocurcumin and tetrahydrocurcumin, which exhibit antioxidant and anti-inflammatory properties. Studies suggest that curcumin can reduce body mass index (BMI) and improve other body composition parameters, especially when used in combination with lifestyle changes, though its bioavailability is low due to its rapid metabolism and the resulting low blood concentration. In obesity, dysfunctional adipose tissue remodeling and chronic inflammation play critical roles in the development of metabolic complications. Curcumin's anti-inflammatory properties are related to the inhibition of the NF-κB pathway, leading to the reduction in inflammatory markers in adipocytes and macrophages. Additionally, curcumin modulates oxidative stress by activating the NRF2 pathway, enhancing cellular antioxidant defenses. Emerging evidence also supports curcumin's potential in improving gut health by modulating microbiota composition, enhancing intestinal barrier function, and reducing systemic inflammation. This interaction with the gut-brain axis highlights the broader implications of curcumin in neuroprotection, as it positively affects cognitive function and mitigates neuroinflammation in neurodegenerative diseases like Alzheimer's. disease. Thus, curcumin holds promise as a multifaceted agent in the management of obesity and associated diseases.

Aging is associated with fat atrophy and fibrosis with loss of adipocyte differentiation from preadipocytes. New approaches to this loss involve agents that can renew the proliferative and differentiative capacities of preadipocytes with the aim of creating new healthy adipose tissue that secrete adipokines that positively impact on skin health.

We investigated the effect of Magnolol (ML), a naturally derived compound, on human primary pre-adipocyte viability and proliferation as well as adipogenic gene expression and increase in lipid production. Cell proliferation was assessed using fluorescent signaling, and adipocyte differentiation was monitored by following morphological and microscopic changes. RNA purification and real-time PCR were undertaken to examine gene expression changes, and Oil red O staining was used to confirm adipose cell transformation. Adipokine expression, in particular adiponectin quantification, was also undertaken.

Magnolol, at a relatively low concentration, demonstrated clear adipogenic activity: with a significant increase in preadipocyte proliferation after 48 h and a significant accumulation of adipocytes as demonstrated by oil red staining. Increased gene expression of PLN1 and FABP4 and a significant increase in adiponectin protein expression was demonstrated.

Magnolol stimulates preadipocyte proliferation and conversion to adipokine-producing adipocytes. This has the potential for a positive skin health and volumizing effect if used in a topical formulation.

Introduction: Obesity is increasing worldwide. Due to the unavailability of affordable obesity drugs in most parts of Nigeria, many overweight and obese people rely on medicinal plants to manage obesity. Thus, the aim of this study is to document medicinal plants traditionally used in the treatment and management of obesity in the North Central Zone of Nigeria, determine the plants to which pharmacological assessment of their use in obesity management has not been reported, and assess their toxicity based on the literature. Methods: Semistructured questionnaires and interviews were used to assess sociodemographic information of the 700 herb sellers/practitioners (100 for each state) who consented to participate in the study. Information gathered on plants that are traditionally used in the management of obesity included administration/dosage, method of preparation, plant part used, method of growth, and plant type. The field study was conducted over a one-year period, from March 2018 to March 2019. Reports of pharmacological activity pertaining to obesity as well as toxicity of the plants were obtained from the literature via scientific databases (Scopus, Web of Science, PubMed, Google Scholar, SciFinder, AJOL, PubChem, and other web sources) after the field survey. Results: A total of 39 families and 70 plant species were used to treat or manage obesity. The majority of plant species used resulted in the family Leguminosae. The relative frequency of citation (RFC) and percentage values for the five most frequently used plants were as follows: Citrus aurantifolia (0.0500; 3.56%), Citrus limon (0.0457; 3.26%), Garcinia kola (0.0429; 3.05%), Zingiber officinale (0.0429; 3.05%), and Allium sativum (0.0414; 2.95%). The majority of the medications were prepared as decoctions (50.5%), and cultivated plants (62.86%) were in the majority of plants used. Results showed that 23 plants have no pharmacological report for antiobesity activities while among the five frequently used plants, only Garcinia kola was reported toxic in preclinical models. Conclusions: This paper provides a valuable compilation of the plants used in obesity treatment in the study area by indigenous healers, highlights plants with no reported pharmacological activity pertaining to obesity, and indicates the toxicity profile of used plants. However, further studies on the mechanism of action are warranted, especially where no reports were obtained.

Obesity is characterized by the accumulation of excessive fat, potentially leading to degenerative diseases. Pancreatic lipase, an enzyme responsible for converting 50-70% of dietary fat into monoglycerides, free fatty acids, and various other smaller molecules, plays a crucial role in fat metabolism. Therefore, this study aimed to review selected Indonesian medicinal plants with the potential to inhibit the activity of the pancreatic lipase enzyme. The results showed that kunci pepet (Kaempferiae angustifolia Rosc.), asam gelugur (Garcinia atroviridis), temulawak (Curcuma xanthorrhiza), jombang (Taraxacum officinale F. H. Wigg), pegagan (Centella asiatica), and pala (Myristica fragrans) had strong inhibitory effects, exceeding 50% for both in vitro and in vivo studies. Therefore, further studies are needed to explore the potential of these medicinal plants as anti-obesity treatments.

Several chronic liver injuries can result in liver fibrosis, a wound-healing response defined by an excessive buildup of diffuse extracellular matrix (ECM). Liver fibrosis may progress to liver cirrhosis, liver failure, or hepatocellular carcinoma. Many cellular routes are implicated in the fibrosis process; however, hepatic stellate cells appear to be the main cell type involved. Curcumin, a polyphenolic substance extracted from the Curcuma longa plant, has a diversity of pharmacologic impacts, including anti- inflammatory, antioxidant, antiproliferative and antiangiogenic actions. The anti-fibrotic property of curcumin is less clear, but curcumin's ability to influence inflammatory cytokines, inflammatory pathways, the expression of pro-apoptotic (up-regulated) and anti- apoptotic (down-regulated) proteins, and its ability to lower oxidative stress likely underlie its anti-fibrotic properties. In this review, we investigate and analyze the impact of curcumin on several disorders that lead to liver fibrosis, and discuss the therapeutic applications of curcumin for these disorders.

Adipose tissue is a key regulator of systemic energy homeostasis and improving adipose tissue function provides a brand-new theoretical reference for the prevention and treatment of obesity. FLLL32, a curcumin analog, can hinder various carcinogenic processes, however, its role in adipose tissue has not been fully elucidated. In this study, we observed that FLLL32 treatment significantly improved cold intolerance and reduced white adipose tissue (WAT) adipocyte size in mice, but had no effect on body weight and adipose tissues weight. Furthermore, FLLL32 treatment upregulated the expression level of uncoupling protein 1 and downregulated the expression level of peroxisome proliferator-activated receptor gamma in adipose tissue. Additionally, FLLL32 promoted the mRNA level of transferrin receptor protein 1, a key iron transporter on the cell membrane, and the lipid peroxidation in inguinal WAT. Finally, FLLL32 significantly inhibited the differentiation and maturation of preadipocytes. In summary, our results demonstrated that FLLL32 plays a crucial role in regulating adipose tissue function.

Curcumin, an inherent polyphenolic compound, has the potential to influence glycemic indices. Nevertheless, the conclusions drawn from extant meta-analyses remain contentious. To determine the impact of curcumin supplementation on these indices, the current umbrella meta-analysis included existing systematic reviews and meta-analyses. A thorough systematic search was conducted using databases Embase, PubMed, WOS, Scopus, and the Cochrane Library to acquire peer-reviewed literature published before January 2024. The random-effects model was employed to conduct a meta-analysis. The present analysis incorporated a total of 22 meta-analytic studies. The findings of our study indicate that the administration of curcumin supplements leads to a significant decrease in fasting blood sugar levels (FBS) (ES: -1.63; 95 % CI: -2.36, -0.89, P<0.001; I2=88.4 %, P<0.001), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (ES: -0.38; 95 % CI: -0.48, -0.28, P<0.001; I2=35.9 %, P=0.142), hemoglobin A1c (HbA1c) (ES: -0.44; 95 % CI: -0.67, -0.21, P<0.001; I2=65.0 %, P=0.014), and insulin (ES: -0.86; 95 % CI: -1.52, -0.21, P=0.010; I2=92.5 %, P<0.001). The results of this study suggest that the administration of curcumin supplements may be a beneficial intervention for enhancing glycemic indices.

The gut microbiome plays a critical role in maintaining gut and metabolic health, and its composition is often altered by aging and obesity. This study aimed to investigate the protective effects of curcumin on gut dysbiosis, gut barrier integrity, and bile acid homeostasis in aged mice fed a high-fat, high-sugar diet (HFHSD). Eighteen- to twenty-one-month-old male C57BL/6 mice were divided into groups fed a normal chow diet or HFHSD, with or without curcumin supplementation (0.4% w/w) for 8 and 15 weeks. We assessed body weight, food intake, insulin sensitivity, gut microbiota composition, and gene expression in the gut and liver and performed histological analysis of gut tissues. Curcumin supplementation prevented HFHSD-induced weight gain and metabolic disturbances. In the gut, curcumin-treated mice showed a higher abundance of beneficial bacterial genera, such as Lachnospiraceae, Akkermansia, Mucispirillum, and Verrucomicrobiota, alongside a lower abundance of harmful bacterial genera like Desulfobacteria, Alistipes, and Muribaculaceae compared to control. This shift in gut microbiota was associated with improved gut integrity, as demonstrated by increased expression of the tight junction protein occludin and reduced levels of the pro-inflammatory marker interleukin-1β in the ileum. Additionally, curcumin modulated hepatic gene expression involved in bile acid homeostasis, suggesting a positive effect on liver health. Curcumin supplementation can alleviate the negative effects of aging and an HFHSD on the gut microbiome, improve gut barrier integrity, and maintain bile acid homeostasis. These findings highlight curcumin's potential as a dietary intervention for managing obesity- and age-associated gut health issues.

Excess weight gain is a growing concern worldwide, fueled by increased consumption of calorie-dense foods and more sedentary lifestyles. Obesity in China is also becoming increasingly problematic, developing into a major public health concern. Obesity not only increases the risk of associated disease but also imposes a burden on health care systems, and it is thus imperative that an effective intervention approach be identified. Recent studies have demonstrated that the polyphenol-rich Mediterranean diet has considerable potential in this regard. Polyphenols can inhibit the production of adipocytes and reduce adverse reactions, such as inflammation, insulin resistance, and gut microflora imbalance. In this review, we examine four polyphenols (curcumin, ellagic acid, ferulic acid, and quercetin) in terms of their potential as interventions targeting obesity. The mechanisms that help promote adipocyte browning, increase thermogenic factors, increase thermogenesis, and regulate adipocyte differentiation are summarized, and key signaling pathways, including PPARγ, C/EBP-, and others, are reviewed.

Lipotoxicity is defined as a prolonged metabolic imbalance of lipids that results in ectopic fat distribution in peripheral organs such as the liver, heart, and kidney. The harmful consequences of excessive lipid accumulation in cardiomyocytes cause cardiac lipotoxicity, which alters the structure and function of the heart. Obesity and diabetes are linked to lipotoxic cardiomyopathy. These anomalies might be caused by a harmful metabolic shift that accumulates toxic lipids and shifts glucose oxidation to less fatty acid oxidation. Research has linked fatty acids, fatty acyl coenzyme A, diacylglycerol, and ceramide to lipotoxic stress in cells. This stress can be brought on by apoptosis, impaired insulin signaling, endoplasmic reticulum stress, protein kinase C activation, p38 Ras-mitogen-activated protein kinase (MAPK) activation, or modification of peroxisome proliferator-activated receptors (PPARs) family members. Curcuma longa is used to extract curcumin, a hydrophobic polyphenol derivative with a variety of pharmacological characteristics. Throughout the years, curcumin has been utilized as an anti-inflammatory, antioxidant, anticancer, hepatoprotective, cardioprotective, anti-diabetic, and anti-obesity drug. Curcumin reduces cardiac lipotoxicity by inhibiting apoptosis and decreasing the expression of apoptosis-related proteins, reducing the expression of inflammatory cytokines, activating the autophagy signaling pathway, and inhibiting the expression of endoplasmic reticulum stress marker proteins.

Repositioning of FDA approved/clinical phase drugs has recently opened a new opportunity for rapid approval of drugs, as it shortens the overall process of drug discovery and development. In previous studies, we predicted the possibility of better activity profiles of flavopiridol, the FDA approved orphan drug with better fit value 2.79 using a common feature pharmacophore model for anti-adipogenic compounds (CFMPA). The present study aimed to investigate the effect of flavopiridol on adipocyte differentiation and to determine the underlying mechanism. Flavopiridol inhibited adipocyte differentiation in different cell models like 3T3-L1, C3H10T1/2, and hMSCs at 150 nM. Flavopiridol was around 135 times more potent than its parent molecule rohitukine. The effect was mediated through down-regulation of key transcription factors of adipogenesis i.e. Peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and their downstream targets, including adipocyte protein -2 (aP2) and fatty acid synthase (FAS). Further, results revealed that flavopiridol arrested the cell cycle in G1/S phase during mitotic clonal expansion by suppressing cell cycle regulatory proteins i.e. Cyclins and CDKs. Flavopiridol inhibited insulin-stimulated signalling in the early phase of adipocyte differentiation by downregulation of AKT/mTOR pathway. In addition, flavopiridol improved mitochondrial function in terms of increased oxygen consumption rate (OCR) in mature adipocytes. In the mouse model of diet-induced obesity, flavopiridol attenuated obesity-associated adipose tissue inflammation and improved serum lipid profile, glucose tolerance as well as insulin sensitivity. In conclusion, the FDA approved drug flavopiridol could be placed as a potential drug candidate for the treatment of cancer and obesity comorbid patients.

Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver β-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.

Over the past five decades, Curcumin (Cur), derived from turmeric (Curcuma longa), has gained considerable attention for its potential therapeutic applications. Synthesizing insights from clinical trials conducted over the last 25 years, this review delves into diseases where Cur has demonstrated promise, offering a nuanced understanding of its pharmacokinetics, safety, and effectiveness. Focusing on specific examples, the impact of Cur on various human diseases is explored. Endocrine glands and associated signaling pathways are highlighted, elucidating how Cur influences cellular signaling. The article underscores molecular mechanisms such as hormone level alteration, receptor interaction, cytokine and adipokine expression inhibition, antioxidant enzyme activity, and modulation of transcription factors. Cur showcases diverse protective mechanisms against inflammation and oxidative damage by suppressing antiapoptotic genes and impeding tumor promotion. This comprehensive overview emphasizes the potential of Cur as a natural agent for countering aging and degenerative diseases, calling for further dedicated research in this realm.

Obesity and Type 2 diabetes are prevalent metabolic dysfunctions that present significant health challenges worldwide. Available cures for these ailments have constraints with accompanying unwanted effects that persistently exist. Compounds originated from plants have recently been introduced as hopeful remedies to treat metabolic disorders because of their diverse pharmacological activities. This detailed observation gives an introduction into the treatment capacity of plant-derived compounds regarding metabolic syndromes while analyzing various groups alongside their performance in this field despite unique mechanisms designed by nature itself. Interestingly, this study provides some examples including curcumin, resveratrol, quercetin, berberine, epigallocatechin gallate (EGCG), and capsaicin, which highlights potential therapeutic impacts for future testing. However, current clinical trials inspecting human studies investigating efficacies concerning metabolism challenge present limitations. Finally, the review weighs up bad reactions possibly inflicted after administering plant-originated materials though suggestive insights will be provided later. Above all, it outlines the chance to identify novel therapies encapsulated within natural substances based upon recent developments could hold significant promise toward managing misplaced metabolisms globally.

Uterine fibroids (UFs) are the most common prevalent benign tumor among women of reproductive age, disproportionately affecting women of color. This paper introduces an innovative management strategy for UFs, emphasizing the curbing of disease prevention and progression. Traditionally, medical intervention is deferred until advanced stages, necessitating invasive surgeries such as hysterectomy or myomectomy, leading to high recurrence rates and increased healthcare costs. The strategy, outlined in this review, emphasizes UF disease management and is named LIFE UP awareness-standing for Lifestyle Interventions, Food Modifications, and Environmental Practices for UF Prevention. These cost-effective, safe, and accessible measures hold the potential to prevent UFs, improve overall reproductive health, reduce the need for invasive procedures, and generate substantial cost savings for both individuals and healthcare systems. This review underscores the importance of a proactive UF management method, paving the way for future research and policy initiatives in this domain.

Curcumin, a natural polyphenolic component from Curcuma longa roots, is the main bioactive component of turmeric spice and has gained increasing interest due to its proposed anti-cancer, anti-obesity, anti-inflammatory, antioxidant, and lipid-lowering effects, in addition to its thermogenic capacity. While intake from dietary sources such as curry may be sufficient to affect the intestinal microbiome and thus may act indirectly, intact curcumin in the body may be too low (<1 microM) and not sufficient to affect signaling and gene expression, as observed in vitro with cultured cells (10-20 microM). Several strategies can be envisioned to increase curcumin levels in the body, such as decreasing its metabolism or increasing absorption through the formation of nanoparticles. However, since high curcumin levels could also lead to undesired regulatory effects on cellular signaling and gene expression, such studies may need to be carefully monitored. Here, we review the bioavailability of curcumin and to what extent increasing curcumin levels using nanoformulations may increase the bioavailability and bioactivity of curcumin and its metabolites. This enhancement could potentially amplify the disease-preventing effects of curcumin, often by leveraging its robust antioxidant properties.

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.

Obesity is a major risk factor for morbidity and mortality because it has a close relationship to metabolic illnesses, such as diabetes, cardiovascular diseases, and some types of cancer. With no drugs available, the mainstay of obesity management remains lifestyle changes with exercise and dietary modifications. In light of the tremendous disease burden and unmet therapeutics, fresh perspectives on pathophysiology and drug discovery are needed. The development of epigenetics provides a compelling justification for how environmental, lifestyle, and other risk factors contribute to the pathogenesis of obesity. Furthermore, epigenetic dysregulations can be restored, and it has been reported that certain natural products obtained from plants, such as tea polyphenols, ellagic acid, urolithins, curcumin, genistein, isothiocyanates, and citrus isoflavonoids, were shown to inhibit weight gain. These substances have great antioxidant potential and are of great interest because they can also modify epigenetic mechanisms. Therefore, understanding epigenetic modifications to target the primary cause of obesity and the epigenetic mechanisms of anti-obesity effects with certain phytochemicals can prove rational strategies to prevent the disease and develop novel therapeutic interventions. Thus, the current review aimed to summarize the epigenetic mechanisms and advances in therapies for obesity based on natural products to provide evidence for the development of several potential anti-obesity drug targets.

Cinchonine is one of the Cinchona alkaloids that is commercially extracted from the Peruvian bark of Cinchona officinalis L. (Family: Rubiaceae). It is also obtained in much lower quantities from other species of Cinchona, such as Cinchona calisaya, Cinchona succirubra, and Cinchona pubescens, and in some other plants, such as Remijia peruviana. Cinchonine has been historically used as an anti-malarial agent. It also has a wide range of other biological properties, including anti-cancer, anti-obesity, anti-inflammatory, anti-parasitic, antimicrobial, anti-platelet aggregation, and anti-osteoclast differentiation.

This review discusses the pharmacological activity of cinchonine under different experimental conditions, including in silico, in vitro, and in vivo. It also covers the compound's physicochemical properties, toxicological aspects, and pharmacokinetics.

A comprehensive literature search was conducted on multiple online databases, such as PubMed, Scopus, and Google Scholar. The aim was to retrieve a wide range of review/research papers and bibliographic sources. The process involved applying exclusion and inclusion criteria to ensure the selection of relevant and high-quality papers.

Cinchonine has numerous pharmacological properties, making it a promising compound for various therapeutic applications. It induces anti-cancer activity by activating caspase-3 and PARP-1, and triggers the endoplasmic reticulum stress response. It up-regulates GRP78 and promotes the phosphorylation of PERK and ETIF-2α. Cinchonine also inhibits osteoclastogenesis, inhibiting TAK1 activation and suppressing NFATc1 expression by regulating AP-1 and NF-κB. Its potential anti-inflammatory effects reduce the impact of high-fat diets, making it suitable for targeting obesity-related diseases. However, research on cinchonine is limited, and further studies are needed to fully understand its therapeutic potential. Further investigation is needed to ensure its safety and efficacy in clinical applications.

Overall, this review article explains the pharmacological activity of cinchonine, its synthesis, and physicochemical properties, toxicological aspects, and pharmacokinetics.

Bioactive compounds found in various natural sources, such as fruits, vegetables, and herbs, have been studied for their potential benefits in managing obesity and diabetes. These compounds include polyphenols, flavonoids, other antioxidants, fiber, and certain fatty acids. Studies have found that these compounds may improve insulin sensitivity, regulate blood sugar levels, and promote weight loss. However, the effects of these compounds can vary depending on the type and amount consumed, as well as individual factors, such as genetics and lifestyle. Nutraceutical substances have multifaceted therapeutic advantages, and they have been reported to have disease-prevention and health-promoting properties. Several clinically used nutraceuticals have been shown to target the pathogenesis of diabetes mellitus, obesity, and metabolic syndrome and their complications and modulate various clinical outcomes favorably. This review aims to highlight and comment on some of the most prominent natural components used as antidiabetics and in managing obesity.

Dyslipidemia and altered lipid metabolism are closely involved in the pathogenesis and clinical manifestation of many metabolic and non-metabolic diseases. Therefore, mitigation of pharmacological and nutritional factors together with lifestyle modifications is paramount. One potential nutraceutical exhibiting cell signaling and lipid-modulating properties implicated in dyslipidemias is curcumin. Specifically, recent evidence suggest that curcumin may improve lipid metabolism and prevent dyslipidemia-induced cardiovascular complications via several pathways. Although the exact molecular mechanisms involved are not well understood, the evidence presented in this review suggests that curcumin can provide significant lipid benefits via modulation of adipogenesis and lipolysis, and prevention or reduction of lipid peroxidation and lipotoxicity via different molecular pathways. Curcumin can also improve the lipid profile and reduce dyslipidemia- dependent cardiovascular problems by impacting important mechanisms of fatty acid oxidation, lipid absorption, and cholesterol metabolism. Although only limited direct supporting evidence is available, in this review we assess the available knowledge regarding the possible nutraceutical effects of curcumin on lipid homeostasis and its possible impacts on dyslipidemic cardiovascular events from a mechanistic viewpoint.

Obesity is a non-communicable chronic disease that continues to increase around the world. Recently, it has been shown that curcumin positively affects lipid, energy metabolism, and body weight change. Moreover, polyamines are aliphatic polycations, which can be found in all mammalian cells and foods and have been shown to prevent obesity through many different mechanisms. However, whether the co-administration of curcumin and polyamines has synergistic effects has yet to be clarified. Our study aimed to examine the effects of curcumin and polyamines on obesity and to assess the changes in serum polyamine levels and tissue parameters. 28 Sprague-Dawley male rats were fed a high-fat diet for 10 weeks to develop obesity, and then they were randomly divided into 4 groups as the control group (CONT), curcumin group (CUR), polyamine group (POL), curcumin and polyamine group (CUR+POL) and supplements were administered for 6 weeks. As a result, the lowest feed consumption in rats was recorded in the CUR+POL group, and the group with the lowest weight after supplements was the POL group, then the CUR+POL, CONT, and CUR groups, respectively. N-acetyl putrescine and GABA levels increased significantly after obesity development. The total histopathological score in fat, liver, and kidney tissues increased significantly in the CONT group. In the CUR+POL group, damage to the tissues was in the direction of recovery compared to the other groups, and the expression of NF-κB was significantly low. These results suggest that combined curcumin and polyamines may have protective effects.

The reprogramming of lipid metabolism and its association with oncogenic signaling pathways within the tumor microenvironment (TME) have emerged as significant hallmarks of cancer. Lipid metabolism is defined as a complex set of molecular processes including lipid uptake, synthesis, transport, and degradation. The dysregulation of lipid metabolism is affected by enzymes and signaling molecules directly or indirectly involved in the lipid metabolic process. Regulation of lipid metabolizing enzymes has been shown to modulate cancer development and to avoid resistance to anticancer drugs in tumors and the TME. Because of this, understanding the metabolic reprogramming associated with oncogenic progression is important to develop strategies for cancer treatment. Recent advances provide insight into fundamental mechanisms and the connections between altered lipid metabolism and tumorigenesis. In this review, we explore alterations to lipid metabolism and the pivotal factors driving lipid metabolic reprogramming, which exacerbate cancer progression. We also shed light on the latest insights and current therapeutic approaches based on small molecular inhibitors and phytochemicals targeting lipid metabolism for cancer treatment. Further investigations are worthwhile to fully understand the underlying mechanisms and the correlation between altered lipid metabolism and carcinogenesis.

Obesity has reached an epidemic proportion in the last thirty years, and it is recognized as a major health issue in modern society now with the possibility of serious social and economic consequences. By the year 2030, nearly 60% of the global population may be obese or overweight, which emphasizes a need for novel obesity treatments. Various traditional approaches, such as pharmacotherapy and bariatric surgery, have been utilized in clinical settings to treat obesity. However, these methods frequently show the possibility of side effects while remaining ineffective. There is, therefore, an urgent need for alternative obesity treatments with improved efficacy and specificity. Polymeric materials and chemical strategies are employed in emerging drug delivery systems (DDSs) to enhance therapy effectiveness and specificity by stabilizing and controlling the release of active molecules such as natural ingredients. Designing DDSs is currently a top priority research objective with an eye towards creating obesity treatment approaches. In reality, the most recent trends in the literature demonstrate that there are not enough in-depth reviews that emphasize the current knowledge based on the creation and design of DDSs for obesity treatment. It is also observed in the existing literature that a complex interplay of different physical and chemical parameters must be considered carefully to determine the effectiveness of the DDSs, including microneedles, for obesity treatment. Additionally, it is observed that these properties depend on how the DDS is synthesized. Although many studies are at the animal-study stage, the use of more advanced DDS techniques would significantly enhance the development of safe and efficient treatment approaches for obese people in the future. Considering these, this review provides an overview of the current anti-obesity treatment approaches as well as the conventional anti-obesity therapeutics. The article aims to conduct an in-depth discussion on the current trends in obesity treatment approaches. Filling in this knowledge gap will lead to a greater understanding of the safest ways to manage obesity.

Uterine fibroids (UFs) are common tumors in women of reproductive age. It is imperative to comprehend UFs' associated risk factors to facilitate early detection and prevention. Simple relying on surgical/pharmacological treatment of advanced disease is not only highly expensive, but it also deprives patients of good quality of life (QOL). Unfortunately, even if the disease is discovered early, no medical intervention is traditionally initiated until the disease burden becomes high, and only then is surgical intervention performed. Furthermore, after myomectomy, the recurrence rate of UFs is extremely high with the need for additional surgeries and other interventions. This confused approach is invasive and extremely costly with an overall negative impact on women's health. Secondary prevention is the management of early disease to slow down its progression or even halt it completely. The current approach of watchful observation for early disease is considered a major missed opportunity in the literature. The aim of this article is to present an approach named the ESCAPE (Evidence-Based Approach for Secondary Prevention) of UF management. It comprises simple, inexpensive, and safe steps that can arrest the development of UFs, promote overall reproductive health, decrease the number of unnecessary surgeries, and save billions of health care systems' dollars worldwide.

Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1β, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.

RNA modification is considered as an epigenetic modification that plays an indispensable role in biological processes such as gene expression and genome editing without altering nucleotide sequence, but the molecular mechanism of RNA modification has not been discussed systematically in the development of skin diseases. This article mainly presents the whole picture of theoretical achievements on the potential role of RNA modification in dermatology. Furthermore, this article summarizes the latest advances in clinical practice related with RNA modification, including its detection methods and drug development. Based on this comprehensive review, we aim to illustrate the current blind spots and future directions of RNA modification, which may provide new insights for researchers in this field.

Tetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally) (VHFD+THC treated group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), TNF-α, VEGF, MMP-2, and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, TNF-α, VEGF, MMP-2, and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of TNF-α, VEGF, MMP-2, and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of TNF-α, VEGF, MMP-2, and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.

Obesity is a major risk factor for various chronic diseases, especially lifestyle-related diseases. Therefore, finding a protective substance against obesity and elucidating its molecular mechanism is one of the most important problems for improving human health. In this study, we investigated the antiobesity effect of Mallotus furetianus extract (MFE). The aim of the study was to examine the in vivo and in vitro effects of MFE on lipid synthesis. We examined the effect using an in vivo experimental system with obesity model mice and an in vitro experimental system with 3T3-L1 preadipocytes. We found that the treatment of MFE significantly suppressed the increase in body weight and adipose tissue weight and morphological changes in the liver and adipose tissue of the obesity model mice. In the in vitro experimental system, we revealed that MFE treatment suppressed the expression of transcription factors such as C/EBPα, C/EBPβ, and PPARγ, which are involved in the early differentiation of 3T3-L1 preadipocytes. As a result, the ability to synthesize triacylglycerol was suppressed. An interesting finding in this study was the clarification that MFE decreases the expression of C/EBPβ through post-translation modifications (PTMs), followed by the transcriptional suppression of PPAR𝛾 and C/EBP𝛼.

The objective of this study was to evaluate the therapeutic efficacy of the curcumin analogue L6H4 in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats.

Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The rats were then treated with L6H4 for eight weeks. Body weight, metabolic parameters, liver function, and liver histopathology were evaluated. Immunohistochemistry was performed to assess the expression of TGF-β1, TIMP-2, and MMP-2 in liver tissues. Statistical analysis was conducted using one-way ANOVA and Spearman rank correlation test.

L6H4 treatment effectively reversed the weight gain associated with a high-fat diet and improved metabolic parameters in diabetic rats. Liver function markers, such as ALT and AST, were reduced after L6H4 treatment. Histological analysis showed improved liver morphology and reduced fibrosis in L6H4-treated rats. Electron microscopy revealed improved ultrastructural features of hepatocytes. Immunohistochemistry demonstrated downregulation of TGF-β1 and TIMP-2 expression and restoration of MMP-2 expression in the liver tissue of L6H4-treated rats. Correlation analysis showed a significant positive correlation between TGF-β1 and TIMP-2 expression.

The findings suggest that L6H4 has therapeutic potential in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. The hepatoprotective effect of L6H4 may be attributed to its anti-inflammatory properties and its ability to target molecules involved in fibrosis. Further research is warranted to explore the potential of L6H4 as a treatment option for nonalcoholic fatty liver disease and type 2 diabetes.

This experiment aimed to assess the impact of different dietary curcumin (CM) levels on growth, muscle quality, serum-biochemical parameters, antioxidant-enzyme activities, gut microbiome, and liver transcriptome in Chinese soft-shelled turtles (Pelodiscus sinensis). Five experimental diets were formulated to include graded levels of curcumin at 0 (control, CM0), 0.5 (CM0.5), 1 (CM1), 2 (CM2) and 4 g/kg (CM4). Each diet was randomly distributed to quadruplicate groups of turtles (164.33 ± 5.5 g) for 6 weeks. Our findings indicated that dietary curcumin supplementation did not have a significant influence on growth performance (p > 0.05); however, it significantly improved the muscular texture profiles (p < 0.05). Serum total superoxide dismutase (SOD), liver catalase (CAT), and total antioxidant capacity (T-AOC) activities increased significantly as dietary curcumin levels rose from 0.5 to 4 g/kg (p < 0.05). Dietary curcumin supplementation improved gut microbiota composition, as evidenced by an increase in the proportion of dominant bacteria such as Lactobacillus and Flavobacterium. Liver transcriptome analysis revealed that curcumin altered metabolic pathways in the liver. In conclusion, based on the evaluation of the activities of SOD in serum and CAT in liver under current experimental design, it was determined that the appropriate dietary curcumin supplementation for Chinese soft-shelled turtles is approximately 3.9 g/kg.

Dietary patterns are promising strategies for preventing and treating obesity and its coexisting inflammatory processes. Bioactive food compounds have received considerable attention due to their actions against obesity-induced inflammation, with limited harmful side effects. They are perceived as food ingredients or dietary supplements other than those necessary to meet basic human nutritional needs and are responsible for positive changes in the state of health. These include polyphenols, unsaturated fatty acids, and probiotics. Although the exact mechanisms of bioactive food compounds' action are still poorly understood, studies have indicated that they involve the modulation of the secretion of proinflammatory cytokines, adipokines, and hormones; regulate gene expression in adipose tissue; and modify the signaling pathways responsible for the inflammatory response. Targeting the consumption and/or supplementation of foods with anti-inflammatory potential may represent a new approach to obesity-induced inflammation treatment. Nevertheless, more studies are needed to evaluate strategies for bioactive food compound intake, especially times and doses. Moreover, worldwide education about the advantages of bioactive food compound consumption is warranted to limit the consequences of unhealthy dietary patterns. This work presents a review and synthesis of recent data on the preventive mechanisms of bioactive food compounds in the context of obesity-induced inflammation.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder among women (4%-20%) when the ovaries create abnormally high levels of androgens, the male sex hormones that are typically present in women in trace amounts. The primary characteristics of PCOS include oxidative stress, inflammation, hyperglycemia, hyperlipidemia, hyperandrogenism, and insulin resistance. Generally, metformin, spironolactone, eflornithine and oral contraceptives are used to treat PCOS, despite their several side effects. Therefore, finding a potential candidate for treating PCOS is necessary. Curcumin is a major active natural polyphenolic compound derived from turmeric (Curcuma longa). A substantial number of studies have shown that curcumin has anti-inflammatory, anti-oxidative stress, antibacterial, and anti-apoptotic activities. In addition, curcumin reduces hyperglycemia, hyperlipidemia, hyperandrogenism, and insulin resistance in various conditions, including PCOS. The review highlighted the therapeutic aspects of curcumin against the pathophysiology of PCOS. We also offer a hypothesis to improve the development of medicines based on curcumin against PCOS.

Dietary interventions with bioactive compounds have been found to suppress the accumulation of senescent cells and senescence-associated secretory phenotypes (SASPs). One such compound, curcumin (CUR), has beneficial health and biological effects, including antioxidant and anti-inflammatory properties, but its ability to prevent hepatic cellular senescence is unclear. The objective of this study was to investigate the effects of dietary CUR as an antioxidant on hepatic cellular senescence and determine its benefits on aged mice. We screened the hepatic transcriptome and found that CUR supplementation led to the downregulation of senescence-associated hepatic gene expressions in both usually fed and nutritionally challenged aged mice. Our results showed that CUR supplementation enhanced antioxidant properties and suppressed mitogen-activated protein kinase (MAPK) signaling cascades in the liver, particularly c-Jun N-terminal kinase (JNK) in aged mice and p38 in diet-induced obese aged mice. Furthermore, dietary CUR decreased the phosphorylation of nuclear factor-κB (NF-κB), a downstream transcription factor of JNK and p38, and inhibited the mRNA expression of proinflammatory cytokines and SASPs. The potency of CUR administration was demonstrated in aged mice via enhanced insulin homeostasis along with declined body weight. Taken together, these results suggest that CUR supplementation may be a nutritional strategy to prevent hepatic cellular senescence.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Curcumin is a natural polyphenol that may be effective against liver steatosis and steatohepatitis. The present study aimed to evaluate the effects of phytosomal curcumin on lipid profile, fasting blood sugar, anthropometric indices, liver enzymes, fibrosis, and steatosis in non-alcoholic fatty liver patients.

The participants were randomized to the curcumin-phosphatidylserine phytosomal receiving group and the placebo receiving group and were followed up for 12 weeks. Data on anthropometric indices, lipid profile, blood glucose, blood pressure, liver enzymes, hepatic steatosis, and fibrosis were collected at the beginning and the end of the clinical trial.

Supplementation for 12 weeks with phytosomal curcumin significantly reduced fibrosis and steatosis in the phytosomal curcumin receiving group compared with the placebo group (p < 0.05). Phytosomal curcumin also significantly reduced waist circumference and blood pressure compared with the placebo group (p < 0.05). There was no significant difference between the phytosomal curcumin and the placebo groups regarding changes in weight, body mass index, fasting blood glucose, liver enzymes, and lipid profile.

Curcumin, at a dose of 250 mg per day, might be effective in treating patients with NAFLD. Further studies are necessary to confirm these findings and to discover the underlying mechanisms.

https://www.irct.ir/trial/43730, identifier: IRCT20121216011763N39.

The adaptive response to overfeeding is associated with profound modifications of gene expression in adipose tissue to support lipid storage and weight gain. The objective of this study was to assess in healthy lean men whether a supplementation with polyphenols could interact with these molecular adaptations. Abdominal subcutaneous adipose tissue biopsies were sampled from 42 subjects participating to an overfeeding protocol providing an excess of 50% of their total energy expenditure for 31 days, and who were supplemented with 2 g/day of grape polyphenols or a placebo. Gene expression profiling was performed by RNA sequencing. Overfeeding led to a modification of the expression of 163 and 352 genes in the placebo and polyphenol groups, respectively. The GO functions of these genes were mostly involved in lipid metabolism, followed by genes involved in adipose tissue remodeling and expansion. In response to overfeeding, 812 genes were differentially regulated between groups. Among them, a set of 41 genes were related to angiogenesis and were downregulated in the polyphenol group. Immunohistochemistry targeting PECAM1, as endothelial cell marker, confirmed reduced angiogenesis in this group. Finally, quercetin and isorhamnetin, two polyphenol species enriched in the plasma of the volunteers submitted to the polyphenols, were found to inhibit human umbilical vein endothelial cells migration in vitro. Polyphenol supplementation do not prevent the regulation of genes related to lipid metabolism in human adipose tissue during overfeeding, but impact the angiogenesis pathways. This may potentially contribute to a protection against adipose tissue expansion during dynamic phase of weight gain.

Metabolic syndrome is characterized by multiple metabolic disorders. Several studies indicated that curcumin plus piperine could affect lipids profiles in various diseases. The present meta-analysis aims to assess the effect of curcumin plus piperine on lipid profiles in patients with MetS and associated disorders using a systematic review and meta-analysis of randomized controlled trials. Trials were searched by several electronic databases up to May 2022. The Comprehensive Meta-Analysis (CMA) version3 software carried out this systematic review and meta-analysis. Random-effects model and the inverse variance method were used to conduct the meta-analysis. We evaluated the publication bias and heterogeneity of all eligible studies. In addition, subgroup analyses and sensitivity assessments were performed to assess potential sources of heterogeneity. The combined results by the random-effects model demonstrated that curcumin plus piperine significantly decreased total cholesterol and LDL-C in patients suffering from metabolic syndrome. In comparison, the results of the overall effect size did not show any significant change in triglyceride concentrations. Our results were robust in sensitivity analysis and were not dependent on the dose of curcumin, the dose of piperine, and the duration of treatment. Our results showed that co-administration of piperine and curcumin supplementation improves the lipid profile in metabolic syndrome. However, further long-term RCTs are required to ascertain their clinical benefit.

Maternal obesity and dietary style in the pregnancy-lactation period may result in long-term effects on the metabolic health of the offspring, thus increasing the risk of diseases, such as obesity, diabetes, and cardiovascular diseases. Curcumin is a natural polyphenolic compound that has beneficial properties on metabolism. Accordingly, this study is intended to evaluate the effects of curcumin supplementation in pregnant and lactating female mice on the anthropometric, metabolic and molecular parameters of the offspring fed a hyperglycemic diet. The study was conducted with 24 male mice randomized into three groups: i) control group (SD) originating from dams fed a standard diet; ii) hyperglycemic group (HGD) originating from dams fed a hyperglycemic diet; iii) curcumin group (CUR) originating from dams fed a hyperglycemic diet and supplemented with curcumin in the pregnancy-lactation period. All offspring groups were fed a hyperglycemic diet for 12 weeks. Anthropometricand biochemical parameters were measured, as well as the expression of thermogenesis-associated markers in the interscapular brown and inguinal white adipose tissues. The results showed less weight gain in the CUR group, with a concomitant reduction in food consumption compared to the HGD group. Biochemical parameters indicated lower levels of total cholesterol, glucose, and insulin for the CUR group, in addition to improved glucose tolerance and insulin sensitivity. The molecular evaluation indicated increased mRNA expression levels of UCP1 and PRDM16 in the brown and white adipose tissues. It is concluded that curcumin supplementation in the pregnancy-lactation period in dams with diet-induced obesity may lead to improvements in the offspring's metabolic phenotype, even if they are submitted to an obesogenic environment, possibly via thermogenesis activation.

Sirtuins (SIRTs 1-7) are a group of histone deacetylase enzymes with a wide range of enzyme activities that target a range of cellular proteins in the nucleus, cytoplasm, and mitochondria for posttranslational modifications by acetylation (SIRT1, 2, 3, and 5) or ADP ribosylation (SIRT4, 6, and 7). A variety of cellular functions, including mitochondrial functions and functions in energy homeostasis, metabolism, cancer, longevity and ageing, are regulated by sirtuins. Compromised sirtuin functions and/or alterations in the expression levels of sirtuins may lead to several pathological conditions and contribute significantly to alterations in metabolic phenotypes as well as oral carcinogenesis. Here, we describe the basic characteristics of seven mammalian sirtuins. This review also emphasizes the key molecular mechanisms of sirtuins in metabolic regulation and discusses the possible relationships of sirtuins with oral cancers. This review will provide novel insight into new therapeutic approaches targeting sirtuins that may potentially lead to effective strategies for combating oral malignancies.

The prevalence of obesity and its associated diseases has increased dramatically, and they are major threats to human health worldwide. A variety of approaches, such as physical training and drug therapy, can be used to reduce weight and reverse associated diseases; however, the efficacy and the prognosis are often unsatisfactory. It has been reported that natural food-based small molecules can prevent obesity and its associated diseases. Among them, alkaloids and polyphenols have been demonstrated to regulate lipid metabolism by enhancing energy metabolism, promoting lipid phagocytosis, inhibiting adipocyte proliferation and differentiation, and enhancing the intestinal microbial community to alleviate obesity. This review summarizes the regulatory mechanisms and metabolic pathways of these natural small molecules and reveals that the binding targets of most of these molecules are still undefined, which limits the study of their regulatory mechanisms and prevents their further application. In this review, we describe the use of Discovery Studio for the reverse docking of related small molecules and provide new insights for target protein prediction, scaffold hopping, and mechanistic studies in the future. These studies will provide a theoretical basis for the modernization of anti-obesity drugs and promote the discovery of novel drugs.