Underlying Mechanisms behind the Brain-Gut-Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update.

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain-gut-liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain-gut-liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.

Green coffee: economic relevance and a systematic review of the effects on human health.

Coffee is probably the most popular beverage after water and is an important component in diet and health since its consumption is high worldwide. Globally, it is the most relevant food commodity being just behind crude oil. Besides its pleasant flavor, it is an antioxidant source due to polyphenols, which are protective compounds against several diseases. This study aimed to evaluate the economic relevance and perform a systematic review of green coffee's effects on human health. Databases such as MEDLINE-PubMed, EMBASE, COCHRANE, and GOOGLE SCHOLAR were searched, and PRISMA guidelines were followed. Green coffee is considered a novel food product because consumers usually consume only roasted coffee. It can be marketed as such or as an extract. Due to the content of bioactive compounds, which are partially lost during the roasting process, the extracts are usually marketed concerning the potential regarding health effects. Green coffee can be used as dietary supplements, cosmetics, and pharmaceuticals, as a source of antioxidants. It can benefit human health, such as improvement in blood pressure, plasma lipids, and body weight (thus contributing to the improvement of risk components of Metabolic Syndrome). Moreover, benefits for cognitive functions may also be included.

Avocado (Persea americana Mill) and its phytoconstituents: potential for cancer prevention and intervention.

Dietary compounds, including fruits, vegetables, nuts, and spices, have been shown to exhibit anticancer properties due to their high concentrations of vitamins, minerals, fiber, and secondary metabolites, known as phytochemicals. Although emerging studies suggest that avocado (Persea americana Mill) displays antineoplastic properties in addition to numerous other health benefits, current literature lacks an updated comprehensive systematic review dedicated to the anticancer effects of avocado. This review aims to explore the cancer-preventive effects of avocados and the underlying molecular mechanisms. The in vitro studies suggest the various avocado-derived products and phytochemicals induced cytotoxicity, reduced cell viability, and inhibited cell proliferation. The in vivo studies revealed reduction in tumor number, size, and volume as well. The clinical studies demonstrated that avocado leaf extract increased free oxygen radical formation in larynx carcinoma tissue. Various avocado products and phytochemicals from the avocado fruit, including avocatin-B, persin, and PaDef defensin, may serve as viable cancer prevention and treatment options based on current literature. Despite many favorable outcomes, past research has been limited in scope, and more extensive and mechanism-based in vivo and randomized clinical studies should be performed before avocado-derived bioactive phytochemicals can be developed as cancer preventive agents.

Garlic: A systematic review of the effects on cardiovascular diseases.

Allium sativum (garlic) certainly is one of the oldest horticultural crops in the world and presents bioactive compounds that are related to the garlic's effects on human health. Several authors have shown beneficial effects on diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases (CVD), which are among the most relevant causes of mortality in the world. The aim of this systematic review was to evaluate the effects of garlic in the risk factors of CVD and evaluate its economic importance. MEDLINE-PubMed, COCHRANE, EMBASE, and Google Scholar databases were searched. The included studies showed that the use of garlic can reduce blood pressure, waist circumference, body mass index, LDL-c, non-HDL-c, total cholesterol, triglycerides, and inflammatory markers. It also can increase the levels of HDL-c and can improve cardiovascular parameters such as coronary artery calcium, microcirculation, epicardial and periaortic adipose tissue, post occlusive reactive hyperemia, low attenuation plaque, carotid intima-media thickness; and carotid intima-media thickness. Due to these reasons, garlic can be considered in the prevention and treatment of CVD risk factors.

Effects of Vitamin D Supplementation in Diabetic Kidney Disease: An Systematic Review.

Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.

Metabolic syndrome and cardiovascular diseases: Going beyond traditional risk factors.

Metabolic syndrome (MS) is a chronic non-infective syndrome characterised clinically by a set of vascular risk factors that include insulin resistance, hypertension, abdominal obesity, impaired glucose metabolism, and dyslipidaemia. These risk factors are due to a pro-inflammatory state, oxidative stress, haemodynamic dysfunction, and ischaemia, which overlap in 'dysmetabolic' patients. This review aimed to evaluate the relationship between the traditional components of MS with cardiovascular disease (CVD), inflammation, and oxidative stress. MEDLINE-PubMed, EMBASE, and Cochrane databases were searched. Chronic low-grade inflammatory states and metaflammation are often accompanied by metabolic changes directly related to CVD incidence, such as diabetes mellitus, hypertension, and obesity. Moreover, the metaflammation is characterised by an increase in the serum concentration of pro-inflammatory cytokines, mainly interleukin-1 ß (IL-1ß), IL-6, and tumour necrosis factor-α (TNF-α), originating from the chronically inflamed adipose tissue and associated with oxidative stress. The increase of reactive oxygen species overloads the antioxidant systems causing post-translational alterations of proteins, lipids, and DNA leading to oxidative stress. Hyperglycaemia contributes to the increase in oxidative stress and the production of advanced glycosylation end products (AGEs) which are related to cellular and molecular dysfunction. Oxidative stress and inflammation are associated with cellular senescence and CVD. CVD should not be seen only as being triggered by classical MS risk factors. Atherosclerosis is a multifactorial pathological process with several triggering and aetiopathogenic mechanisms. Its medium and long-term repercussions, however, invariably constitute a significant cause of morbidity and mortality. Implementing preventive and therapeutic measures against oxy-reductive imbalances and metaflammation states has unquestionable potential for favourable clinical outcomes in cardiovascular medicine.

Curcumin, autoimmune and inflammatory diseases: going beyond conventional therapy - a systematic review.

Autoimmune and inflammatory diseases affect innumerous people and are considered a significant cause of morbidity and mortality worldwide and Curcuma sp can work as important therapies in the approach of these diseases. For this reason the aim of this review is to evaluate the effects of Curcuma or curcumin in five autoimmune and/or inflammatory diseases for instance, Inflammatory Bowel Disease, Osteoarthritis, Systemic Lupus Erythematous, Psoriasis, and Sclerosis. MEDLINE, EMBASE, and Cochrane Library were searched and PRISMA guidelines were used to build this systematic review. Curcuma sp or curcumin have been gaining ground in the treatment of autoimmune and inflammatory diseases due to the wide range of bioactive compounds capable of exerting substantial anti-inflammatory and antioxidant actions. The effects can be associated with improvement of symptoms and induction of remission in Inflammatory Bowel Disease patients; reduction of erythema and induration of lesions in psoriasis; and slow down the disease progression in patients with sclerosis. Furthermore, curcumin shows effects equivalent to ibuprofen and diclofenac, without the adverse effects generally reported by patients. Curcuma or its derivatives can be used safely and efficiently as adjuvants or as a main therapy for these diseases that increase year by year in the world population.

The use of vitamin D for patients with inflammatory bowel diseases.

As Vitamin D (VD) plays an essential role in Inflammatory Bowel Diseases, this systematic review aimed to update the participation of this vitamin in the prevention or remission of these diseases. This review has included studies in MEDLINE-PubMed, EMBASE, and Cochrane databases. The authors have followed PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) guidelines. According to the inclusion and exclusion criteria, twenty-two randomized clinical trials were selected. In all, 1,209 patients were included in this systematic review: 1034 received only VD and 175 received VD in combination with calcium. The average doses of VD supplementation were from oral 400 IU daily to 10,000 IU per kilogram of body weight. Single injection of 300,000 IU of VD was also used. Several studies have shown the crucial role that VD plays in the therapeutic approach of IBD due to its effects on the immune system. It effectively decreased inflammatory cytokines such as TNF-α and IFN-γ (p<0.05) and provided a reduction in disease activity assessed through different scores such as Crohn's Disease Activity Index (CDAI) (p<0.05) and Ulcerative Colitis Disease Activity Index (UCDAI) (p<0.05). Unfortunately, the available clinical trials do not have standardization of doses and routes of administration. Existing meta-analyses are biased because they compare studies using different doses or treatments in combination with different drugs or supplements such as calcium. Even though VD has crucial effects on inflammatory processes, there is still a need for standardized studies to establish how the supplementation should be performed and the doses to be administered.

Organokines in Rheumatoid Arthritis: A Critical Review.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects the joints. Organokines can produce beneficial or harmful effects in this condition. Among RA patients, organokines have been associated with increased inflammation and cartilage degradation due to augmented cytokines and metalloproteinases production, respectively. This study aimed to perform a review to investigate the role of adipokines, osteokines, myokines, and hepatokines on RA progression. PubMed, Embase, Google Scholar, and Cochrane were searched, and 18 studies were selected, comprising more than 17,000 RA patients. Changes in the pattern of organokines secretion were identified, and these could directly or indirectly contribute to aggravating RA, promoting articular alterations, and predicting the disease activity. In addition, organokines have been implicated in higher radiographic damage, immune dysregulation, and angiogenesis. These can also act as RA potent regulators of cells proliferation, differentiation, and apoptosis, controlling osteoclasts, chondrocytes, and fibroblasts as well as immune cells chemotaxis to RA sites. Although much is already known, much more is still unknown, principally about the roles of organokines in the occurrence of RA extra-articular manifestations.

GLP-1a: Going beyond Traditional Use.

Glucagon-like peptide-1 (GLP-1) is a human incretin hormone derived from the proglucagon molecule. GLP-1 receptor agonists are frequently used to treat type 2 diabetes mellitus and obesity. However, the hormone affects the liver, pancreas, brain, fat cells, heart, and gastrointestinal tract. The objective of this study was to perform a systematic review on the use of GLP-1 other than in treating diabetes. PubMed, Cochrane, and Embase were searched, and the PRISMA guidelines were followed. Nineteen clinical studies were selected. The results showed that GLP-1 agonists can benefit defined off-medication motor scores in Parkinson's Disease and improve emotional well-being. In Alzheimer's disease, GLP-1 analogs can improve the brain's glucose metabolism by improving glucose transport across the blood-brain barrier. In depression, the analogs can improve quality of life and depression scales. GLP-1 analogs can also have a role in treating chemical dependency, inhibiting dopaminergic release in the brain's reward centers, decreasing withdrawal effects and relapses. These medications can also improve lipotoxicity by reducing visceral adiposity and decreasing liver fat deposition, reducing insulin resistance and the development of non-alcoholic fatty liver diseases. The adverse effects are primarily gastrointestinal. Therefore, GLP-1 analogs can benefit other conditions besides traditional diabetes and obesity uses.

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future.

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.

Organokines, Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise.

Sarcopenia is a disease that becomes more prevalent as the population ages, since it is directly linked to the process of senility, which courses with muscle atrophy and loss of muscle strength. Over time, sarcopenia is linked to obesity, being known as sarcopenic obesity, and leads to other metabolic changes. At the molecular level, organokines act on different tissues and can improve or harm sarcopenia. It all depends on their production process, which is associated with factors such as physical exercise, the aging process, and metabolic diseases. Because of the seriousness of these repercussions, the aim of this literature review is to conduct a review on the relationship between organokines, sarcopenia, diabetes, and other metabolic repercussions, as well the role of physical exercise. To build this review, PubMed-Medline, Embase, and COCHRANE databases were searched, and only studies written in English were included. It was observed that myokines, adipokines, hepatokines, and osteokines had direct impacts on the pathophysiology of sarcopenia and its metabolic repercussions. Therefore, knowing how organokines act is very important to know their impacts on age, disease prevention, and how they can be related to the prevention of muscle loss.

A systematic review of the antidepressant effects of curcumin: Beyond monoamines theory.

BACKGROUND: Depression is a severe, chronic, and recurring mental health disorder, which prevalence and morbimortality have increased in recent years. Several theories are proposed to elucidate the mechanisms of depression, such as the involvement of inflammation and the release of cytokines. Alternative treatments have been developed to improve outcomes of the commonly used drugs, and the use of Curcuma longa stands out. Its primary compound is named curcumin that exhibits antioxidant and anti-inflammatory effects. AIMS: Several studies have shown that curcumin may play antidepressant actions and, therefore, this study aimed to perform a systematic review of the antidepressant effects of curcumin to evaluate the impact of this compound in the treatment of this condition. METHODS: This systematic review has included studies available in MEDLINE-PubMed, EMBASE, and Cochrane databases, and the final selection included 10 randomized clinical trials. CONCLUSION: Curcumin improves depressant and anxiety behavior in humans. It can increase monoamines and brain-derived neurotrophic factor levels and may inhibit the production of pro-inflammatory cytokines and neuronal apoptosis in the brain. Systemically, curcumin enhanced insulin sensitivity, reduced cortisol levels, and reversed metabolic abnormalities. Studies with larger samples and standardized dose and formulation are required to demonstrate the benefits of curcumin in depression treatment since there are many variations in this compound's use.

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions.

Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. This study aims to review the crosstalk between adipokines, myokines, and hepatokines. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.

Grape juice or wine: which is the best option?

Grapes used in the wine or juice production are mainly Vitis vinifera and Vitis labrusca and possess high amounts of polyphenolic compounds. These compounds are associated with the reduction of the inflammatory processes, oxidative stress, and protection against cardiovascular diseases. The industrial processes used for juice and wine production may interfere with the antioxidant composition of these products and the effects on human health. The aim of this review is to compare the effects of the consumption of wine or grape juice on cardiovascular risk factors. We used PRISMA guidelines and Medline/PUBMED and EMBASE to perform our search. The main effects of red wine and grape juice in humans were a reduction of body mass index, waist circumference, glycemia, plasma lipid peroxidation, total cholesterol, LDL-c, triglycerides, blood pressure, and homocysteine levels. Both wine and grape juice possess numerous bioactive compounds that are potentially responsible for many beneficial effects on human health. Nevertheless, there is a need for more double-blind, randomized controlled studies comparing the effects of juice and wine consumption without the biases that occur when comparisons are made with different populations, ages, doses, and different types of wine or juice.

Effects of Ginkgo biloba on Diseases Related to Oxidative Stress.

Ginkgo biloba (GB) is one of the most widely used phytotherapeutic products in the world, and its extract has beneficial properties for the treatment of several pathologies, such as diabetic cardiomyopathy, neurodegenerative diseases, cataracts, hearing loss, myocardial lesion, hippocampus neuronal lesions, morphometry testicular changes, and liver damage. This review aims to investigate the effects of GB on diseases related to oxidative stress. Databases such as MEDLINE/PUBMED and EMBASE were consulted, and PRISMA guidelines were used to build the review. This plant has antioxidant properties since it regulates the expression of antioxidant enzymes positively and reduces reactive oxygen and nitrogen species, contributing to the reduction of lipid peroxidation. It also exhibits anti-inflammatory properties, inhibiting the expression of pro-inflammatory cytokines, such as IL-1, IL-6, and TNF-α. In animal models, the use of GB can show positive effects on brain damage, neurodegenerative diseases, myocardial injury, and renal and liver damage. In humans, the positive effects were shown in diabetes, metabolic syndrome, and ischemic colitis. These effects are due to the presence of compounds such as bilobalide, isoramnetina, quercetin, kaempferol, and ginkgolides A, B, and C. For these reasons, GB can be a low-cost alternative to the therapeutic approach of several pathologies since it acts in the prevention, treatment, and inhibition of several complications of common comorbidities.

Physical Exercise and Myokines: Relationships with Sarcopenia and Cardiovascular Complications.

Skeletal muscle is capable of secreting different factors in order to communicate with other tissues. These mediators, the myokines, show potentially far-reaching effects on non-muscle tissues and can provide a molecular interaction between muscle and body physiology. Sarcopenia is a chronic degenerative neuromuscular disease closely related to cardiomyopathy and chronic heart failure, which influences the production and release of myokines. Our objective was to explore the relationship between myokines, sarcopenia, and cardiovascular diseases (CVD). The autocrine, paracrine, and endocrine actions of myokines include regulation of energy expenditure, insulin sensitivity, lipolysis, free fatty acid oxidation, adipocyte browning, glycogenolysis, glycogenesis, and general metabolism. A sedentary lifestyle accelerates the aging process and is a risk factor for developing sarcopenia, metabolic syndrome, and CVD. Increased adipose tissue resulting from the decrease in muscle mass in patients with sarcopenia may also be involved in the pathology of CVD. Myokines are protagonists in the complex condition of sarcopenia, which is associated with adverse clinical outcomes in patients with CVD. The discovery of new pathways and the link between myokines and CVD remain a cornerstone toward multifaceted interventions and perhaps the minimization of the damage resulting from muscle loss induced by factors such as atherosclerosis.

Associations between inflammatory bowel diseases and vitamin D.

Inflammatory Bowel Diseases (IBD) are increasing sharply, and the common medications are not effective for most patients. Vitamin D (VD) has been considerate to reduce inflammatory processes and may be helpful in IBD. The aim of this review was to perform an update on the potential role of VD in the IBD. We performed a search for articles associating VD and IBD published in MEDLINE-PubMed and EMBASE. The focused question used for the search was "What is the association between Inflammatory Bowel Disease and Vitamin D?" The exclusion criteria for this search were studies not in English, editorials, case reports, or poster presentations. VD prevents the inflammatory process such as negatively interfering with the release of Interleukin (IL)-1, IL-6, and Tumour Necrosis Factor-α; enhancing the function of the intestinal epithelial barrier; decreasing the occurrence of apoptosis; stimulating Toll-Like Receptor-4; inducing the production of an antimicrobial peptide in Paneth cells. Furthermore, deficiency of VD is related to the severity of the symptoms and increased the risk of cancer and surgery. In conclusion, VD shows a potential role in the management of IBD, the supplementation is inexpensive, safe, and leads to improvement of the quality of life.

Curcuminoids from Curcuma Longa: New adjuvants for the treatment of crohn's disease and ulcerative colitis?

Crohn's Disease (CD) and Ulcerative Colitis (UC) result from an overreaction of the bowel to multifactorial stimuli leading to discomfort, pain, and it is associated with high morbidity and lethality. The medications commonly used are expensive and associated with multiple side effects. Curcuma longa exerts anti-inflammatory and antioxidant actions and has shown positive effects on CD and UC treatment, possibly due to the presence of curcuminoids. The objective of this review was to evaluate the role of curcuminoids in the treatment of IBD. A search for articles associating curcuminoids and CD and UC was performed using MEDLINE-PubMed. It has been found that curcumin can reduce oxidative stress and inhibit the migration of neutrophils and inducible nitric oxide synthase in the intestine. It may also improve micro and macroscopic lesions, prevent apoptosis of intestinal cells and also induce the restoration of the mitogen-activated protein kinase immune reaction. As the incidence of CD and UC is growing in many populations, there is an urgency to find an appropriate and accessible therapeutic approach to improve quality of life of patients. The use of curcumin is cheap, efficient and associated with no side effects, and may become an alternative to the IBD treatment.

The Potential Role of Medicinal Plants in Bone Regeneration.

BACKGROUND AND CONTEXT: Natural healing of bone lesions once incomplete or delayed bone regeneration represents an important clinical issue and plants possess compounds that may enhance bone healing, and avoid bone losses. OBJECTIVE: The aim of this review is to evaluate the potential role of medicinal plants in the bone regenaration. METHODS/DESIGN: This review has included relevant studies available in MEDLINE-PubMed in the last three years that associated the role of plants in the bone regeneration. The descriptors used were "bone regeneration and plants" and "bone regeneration and medicinal plants". RESULTS: We selected 59 articles, but only 15 studies dovetailed the study objectives of this review. These studies showed that plants have potential in increasing in the osseointegration once their components may downregulate biomarkers such as interleukin (IL)-1ß, IL-6, IL-8, Tumor Necrosis Factor-α, Metalloproteinase 2, and 3. They may also upregulate mediators such as Vascular Endothelial Growth Factor, Transforming-Growing Factor-ß1, Bone Morphogenetic Protein-2, osteocalcin, osteopontin, and type 1 collagen. The control in the production of these cytokines may help bone regeneration. Plant components such as curcumol, caffeic acid, resveratrol, luteolin, and many others may also be useful in bone health once may interfere in Nuclear Factor-κB and Mitogen Activated Protein Kinases, and may modulate Ca2+ signaling, inflammatory mediator genes, and inhibiting osteoclast-mediated bone resorption. CONCLUSION: Many plants possess components that are effective in promoting bone regeneration and new pharmaceutical technology and pharmacological researchers should be performed in order to establish the dose and the appropriate delivery vehicle of administration of the plant or its compounds.