Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent.

With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.

Hyperbaric Oxygen Therapy Reduces Oxidative Stress and Inflammation, and Increases Growth Factors Favouring the Healing Process of Diabetic Wounds.

Hyperbaric oxygen therapy (HBOT) is the clinical application of oxygen at pressures higher than atmospheric pressure. HBOT has been effectively used to manage diverse clinical pathologies, such as non-healing diabetic ulcers. The aim of the present study was to analyse the effects of HBOT on the plasma oxidative and inflammation biomarkers and growth factors in patients with chronic diabetic wounds. The participants received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20, before and 2 h after the HBOT. An additional (control) blood sample was collected 28 days after wound recovery. No significant differences were evident in haematological parameters, whereas the biochemical parameters progressively decreased, which was significant for creatine phosphokinase (CPK) and aspartate aminotransferase (AST). The pro-inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin 1ß (IL-1ß), progressively decreased throughout the treatments. Biomarkers of oxidative stress--plasma protein levels of catalase, extracellular superoxide dismutase, myeloperoxidase, xanthine oxidase, malondialdehyde (MDA) levels and protein carbonyls--were reduced in accordance with wound healing. Plasma levels of growth factors--platelet-derived growth factor (PDFG), transforming growth factor ß (TGF-ß) and hypoxia-inducible factor 1-alpha (HIF-1α)-- were increased as a consequence of HBOT and reduced 28 days after complete wound healing, whereas matrix metallopeptidase 9 (MMP9) progressively decreased with the HBOT. In conclusion, HBOT reduced oxidative and pro-inflammatory mediators, and may participate in activating healing, angiogenesis and vascular tone regulation by increasing the release of growth factors.

An Update of Anthraquinone Derivatives Emodin, Diacerein, and Catenarin in Diabetes.

Diabetes is part of metabolic diseases and is characterized by high blood sugar levels over a prolonged period as result of an insulin-deficient production or an inappropriate response to insulin by our cells. This chronic disease was the direct cause of 1.6 million deaths in 2016 as reported by the World Health Organization. Emodin is a natural product and active ingredient of various Chinese herbs with the chemical formula 1,3,8-trihydroxy-6-methylanthraquinone. Diacerein is another naturally occurring anthraquinone (1,8-diacetoxy-3-carboxyanthraquinone) commonly used as commercial drug to treat osteoarthritis. These two anthraquinone derivatives have been shown to exert antidiabetic activities. Emodin seems to enhance the glucose tolerance and insulin sensibility via activation of PPARγ and modulation of metabolic-related genes. Diacerein seems to decrease inflammatory cytokines and increase insulin secretion enhancing insulin sensibility and therefore improving glucose control. Other naturally occurring anthraquinone derivatives, such as catenarin (1,4,6,8-tetrahydroxy-3-methylanthraquinone), have been shown to have antidiabetic activities although few studies have been performed. The synthesis of new emodin derivatives is increasing, but these new molecules have not been tested for diabetes treatment. In the current work, available literature on anthraquinone derivatives' effects in diabetes disease is reviewed. Moreover, we discuss the chemistry, food sources, bioavailability, and toxicity of the naturally occurring anthraquinone with antidiabetic effects.

Epigenetic targeting of cancer stem cells by polyphenols (cancer stem cells targeting).

Epigenetic alterations are one of the main factors that disrupt the expression of genes and consequently, they have an important role in the carcinogenicity and the progression of different cancers. Cancer stem cells (CSCs) are accountable for the recurrence, metastasis, and therapeutic failure of cancer. The noticeable and specific pathways in CSCs can be organized by epigenetic mechanisms such as DNA methylation, chromatin remodeling, regulatory RNAs, among others. Since epigenetics modifications can be changed and reversed, it is a possible tool for cancer control and treatment. Epigenetic therapies against CSCs are emerging as a very new strategy with a good future expectation to treat cancer patients. Phenolic compounds are a vast group of substances with anticarcinogenic functions, antiinflammatory, and antioxidative activities. It seems these characteristics are related to neutralizing CSCs development, their microenvironment, and metabolism through epigenetic mechanisms. In the current work, the types of epigenetic changes known in these cells are introduced. In addition, some studies about the use of polyphenols acting through a variety of epigenetic mechanisms to counteract these cells will be reviewed. The reported results seem to indicate that the use of these phenolic compounds may be useful for CSCs defeat.

Grape Polyphenols Ameliorate Muscle Decline Reducing Oxidative Stress and Oxidative Damage in Aged Rats.

A large number of studies have demonstrated the implication of oxidative stress (OxS) in the pathogenesis of ageing-related muscle decline and atrophy. The key mechanism is related to the OxS-induced production of free radicals, with the consequent increase in oxidative damage, resulting in affected muscle quality and strength. The present study aimed to evaluate the efficacy of a grape polyphenol-based nutraceutical formulation (Taurisolo®) in reducing the OxS in muscle of aged rats. A group of 16 aged (20 months) rats were orally administered with Taurisolo® (n = 8; 100 mg/kg Taurisolo®) or placebo (n = 8; 50 mg/kg maltodextrin); an additional group of eight young (three months) rats were also treated with placebo. All the treatments were orally administered for 30 days. The activities of antioxidant enzymes, the levels of malondialdehyde (MDA) and nitrotyrosine (N-Tyr) and the expression of OxS- and inflammation-related genes were evaluated on the gastrocnemius muscle. In muscle samples of the treated-group, increased activity of antioxidant enzymes, reduced MDA and N-Tyr levels and increased expression of antioxidant and anti-inflammatory genes were observed in respect to the placebo. Data herein presented suggest that the chronic treatment with Taurisolo® significantly reduces oxidative damage and improves muscle performance in aged rats.

Therapeutic potential of polyphenols in cardiovascular diseases: Regulation of mTOR signaling pathway.

Cardiovascular diseases comprise of non-communicable disorders that involve the heart and/or blood vessels and have become the leading cause of death worldwide with increased prevalence by age. mTOR is a serine/threonine-specific protein kinase which plays a central role in many physiological processes including cardiovascular diseases, and also integrates various proliferative signals, nutrient and energy abundance and stressful situations. mTOR also acts as central regulator during chronic stress, mitochondrial dysfunction and deregulated autophagy which are associated with senescence. Under oxidative stress, mTOR has been reported to exert protective effects regulating apoptosis and autophagy processes and favoring tissue repair. On the other hand, inhibition of mTOR has been suggested to have beneficial effects against atherosclerosis, cardiac hypertrophy and heart failure, and also in extending the lifespan. In this aspect, the use of drugs or natural compounds, which can target mTOR is an interesting approach in order to reduce the number of deaths caused by cardiovascular disease. In the present review, we intend to shed light on the possible effects and molecular mechanism of natural agents like polyphenols via regulating mTOR.

Therapeutic Effects of Hyperbaric Oxygen in the Process of Wound Healing.

Chronic and non-healing wounds, especially diabetic foot ulcers and radiation injuries, imply remarkable morbidity with a significant effect on the quality of life and a high sanitary cost. The management of these wounds requires complex actions such as surgical debris, antibiotic treatment, dressings and even revascularization. These wounds are characterized by poor oxygen supply resulting in inadequate oxygenation of the affected tissue. The adjuvant treatment with hyperbaric oxygen therapy (HBOT) may increase tissue oxygenation favoring the healing of wounds which do not respond to the usual clinical care. The increase in the partial pressure of oxygen contributes to cover the energy demands necessary for the healing process and reduces the incidence of infections. Moreover, the increase in oxygen leads to the production of reactive species with hormetic activity, acting on signaling pathways that modulate the synthesis of inflammation mediators, antioxidants and growth factors which can contribute to the healing process. Studies performed with cell cultures and in animal models seem to demonstrate the beneficial effects of HBOT. However, clinical trials do not show such conclusive results; thus, additional randomized placebo-controlled studies are necessary to determine the real efficacy of HBOT and the mechanism of action for various types of wounds.

Potential Anti-inflammatory Effects of Hesperidin from the Genus Citrus.

BACKGROUND: The benefits of the Mediterranean diet for protecting against many diseases are usually attributed to high consumption of certain foods, characterized by the presence of bioactive substances such as polyphenols. Inflammation plays an important role in the pathogenesis of numerous diseases such as arthritis, allergies or neurodegenerative disorders. Dietary polyphenols constitute a large family of bioactive substances with potential beneficial effects against a broad group of diseases. Citrus fruits and juices are a rich source of vitamin C and flavonoids, with a potential effect on the inflammatory response. OBJECTIVE: The aim was to evidence the potential anti-inflammatory effects of the flavonoids hesperidin for its possible therapeutic application against diverse pathologies. METHOD: In the present review, available literature about the anti-inflammatory effects of hesperidin is reported and discussed. Moreover, we also discuss the chemistry, bioavailability and proposed mechanisms of action of hesperidin. RESULTS: Hesperidin is a flavonoid present in high concentration in citrus species and has numerous biological properties, principally antioxidant and anti-inflammatory. Several studies have been performed in order to evaluate the effects of hesperidin as anti-inflammatory agent using cellular and animal models and few clinical trials. Hesperidin treatment decreased inflammatory mediators and exerted significant antioxidant effects. The molecular basis for its anti-inflammatory effects seems to be mediated by signalling pathways especially the nuclear factor κß pathway. CONCLUSION: Although hesperidin evidenced anti-inflammatory effects, the specific mechanism of action is not completely known and additional studies are required for elucidation of the molecular targets.

Cardioprotective Effects of the Polyphenol Hydroxytyrosol from Olive Oil.

BACKGROUND: The Mediterranean diet includes olive oil as its primary source of fat. This diet is frequently associated to longevity and a lower incidence of chronic diseases due to its biological activities and health effects. Apart from oleic acid, olive oil contains many bioactive components including polyphenols that have been reported to exert antioxidant and anti-inflammatory activities. Polyphenols may almost in part be responsible for the protective effects against cardiovascular diseases associated with olive oil. OBJECTIVE: To review and discuss the available literature on hydroxytyrosol effects as a cardioprotective agent. Moreover, we also discuss the chemistry, nutritional aspects and bioavailability of hydroxytyrosol. RESULTS: Hydroxytyrosol is one of the major phenolic compounds in olive oil and has demonstrated strong radical-scavenging properties. Several studies have been performed in order to look further into the effects of the polyphenol hydroxytyrosol in relation to cardiovascular events and illnesses in animal trials and in vitro. However, no clinical trials have focused on the specific action of hydroxytyrosol and cardiovascular diseases, although some are being undertaken to look at olive oil or olive leaf extract properties. CONCLUSION: Hydroxytyrosol from olive oil exerts antioxidant, anti-inflammatory, anti-platelet aggregation and ati-atherogenic activities in in vitro and animal models. However, its possible therapeutic use in humans requires additional clinical trials.

Antioxidant Response of Chronic Wounds to Hyperbaric Oxygen Therapy.

We analyzed the effects of the clinical hyperbaric oxygen therapy (HBOT) on the plasma antioxidant response and levels of endothelin-1, Interleukine-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic wounds (20.2±10.0 months without healing). They received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20 before and 2 hours after the HBOT. An additional blood sample was collected 1 month after wound recovery. Serum creatine kinase activity decreased progressively in accordance with the wound healing. Plasma catalase activity significantly increased after the first and fifth sessions of HBOT. Plasma myeloperoxidase activity reported significantly lower values after sessions. Plasma VEGF and IL-6 increased after sessions. Endothelin-1 levels were progressively decreasing during the HBOT, being significant at the session 20. Plasma malondialdehyde concentration was significantly reduced at the last session. Both creatine kinase activity and malondialdehyde levels were maintained lower 1 month after wound recovery respect to initial values. In conclusion, HBOT enhanced the plasma antioxidant defenses and may contribute to activate the healing resolution, angiogenesis and vascular tone regulation by increasing the VEGF and IL-6 release and the endothelin-1 decrease, which may be significant factors in stimulating wound healing.

Wound Healing Effects of Curcumin: A Short Review.

Wound healing is a complex process that consists of several phases that range from coagulation, inflammation, accumulation of radical substances, to proliferation, formation of fibrous tissues and collagen, contraction of wound with formation of granulation tissue and scar. Since antiquity, vegetable substances have been used as phytotherapeutic agents for wound healing, and more recently natural substances of vegetable origin have been studied with the attempt to show their beneficial effect on wound treatment. Curcumin, the most active component of rhizome of Curcuma longa L. (common name: turmeric), has been studied for many years due to its bio-functional properties, especially antioxidant, radical scavenger, antimicrobial and anti-inflammatory activities, which play a crucial role in the wound healing process. Moreover, curcumin stimulated the production of the growth factors involved in the wound healing process, and so curcumin also accelerated the management of wound restoration. The aim of the present review is collecting and evaluating the literature data regarding curcumin properties potentially relevant for wound healing. Moreover, the investigations on the wound healing effects of curcumin are reported. In order to produce a more complete picture, the chemistry and sources of curcumin are also discussed.

Tanshinones and mental diseases: from chemistry to medicine.

The prevalence of mental diseases, especially neurodegenerative disorders, is ever-increasing, while treatment options for such disorders are limited and insufficient. In this scarcity of available medication, it is a feasible strategy to search for potential drugs among natural compounds, such as those found in plants. One such plant source is the root of Chinese sage, Salvia miltiorrhiza Bunge (Labiatae), which contains several compounds reported to possess neuroprotective activities. The most important of these compounds are tanshinones, which have been reported to possess ameliorative activity against a myriad of mental diseases such as Alzheimer's disease, cerebral ischemia/reperfusion injury, and glioma, along with promoting neuronal differentiation and manifesting antinociceptive and anticonvulsant outcomes. This review offers a critical evaluation of the utility of tanshinones to treat mental illnesses, and sheds light on the underlying mechanisms through which these naturally occurring compounds confer neuroprotection.

Wound Healing Effect of Curcumin: A Review.

Wound healing is a complex process that consists of several phases that range from coagulation, inflammation, accumulation of radical substances, to proliferation, formation of fibrous tissues and collagen, contraction of wound with formation of granulation tissue and scar. Since antiquity, vegetable substances have been used as phytotherapeutic agents for wound healing, and more recently natural substances of vegetable origin have been studied with the attempt to show their beneficial effect on wound treatment. Curcumin, the most active component of rhizome of Curcuma longa L. (common name: turmeric), has been studied for many years due to its bio-functional properties, especially antioxidant, radical scavenger, antimicrobial and anti-inflammatory activities, which play a crucial role in the wound healing process. Moreover, curcumin stimulated the production of the growth factors involved in the wound healing process, and so curcumin also accelerated the management of wound restoration. The aim of the present review is collecting and evaluating the literature data regarding curcumin properties potentially relevant for wound healing. Moreover, the investigations on the wound healing effects of curcumin are reported. In order to produce a more complete picture, the chemistry and sources of curcumin are also discussed.

Omega-3 Fatty Acids in the Management of Epilepsy.

Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids (PUFAs) with multiple double bonds. Linolenic and alpha-linolenic acids are omega-6 and omega-3 PUFAs, precursors for the synthesis of long-chain PUFAs (LC-PUFAs), such as arachidonic acid (omega-6 PUFA), and eicosapentaenoic and docosahexaenoic acids (omega-3 PUFAs). The three most important omega-3 fatty acids are alpha-linolenic, eicosapentaenoic and docosahexaenoic acids, which cannot be synthesized in enough amounts by the body, and therefore they must be supplied by the diet. Omega-3 fatty acids are essential for the correct functioning of the organism and participate in many physiological processes in the brain. Epilepsy is a common and heterogeneous chronic brain disorder characterized by recurrent epileptic seizures leading to neuropsychiatric disabilities. The prevalence of epilepsy is high achieving about 1% of the general population. There is evidence suggesting that omega-3 fatty acids may have neuroprotective and anticonvulsant effects and, accordingly, may have a potential use in the treatment of epilepsy. In the present review, the potential use of omega-3 fatty acids in the treatment of epilepsy, and the possible proposed mechanisms of action are discussed. The present article summarizes the recent knowledge of the potential protective role of dietary omega-3 fatty acids in epilepsy.

Oxidative status assessment of the endemic bivalve Pinna nobilis affected by the oil spill from the sinking of the Don Pedro.

Several biomarkers were determined to evaluate the effects of the Don Pedro spillage on the digestive gland of the fan mussel Pinna nobilis (Linnaeus, 1758). Two areas in the southeast of Ibiza Island (Western Mediterranean) were selected; one affected by the oil spill (Talamanca) and one did not affected (Espardell). Mussels were sampled one, six and twelve months after the accident. PAH levels were elevated in P. nobilis from the affected area one month after the accident and, although they were decreasing gradually, they were always higher than in the control area. An increase in enzyme activities, reduced glutathione and lipid peroxidation were evidenced one month after the spillage, with no changes in acetylcholinesterase. All biomarkers progressively returned to basal levels one year after the oil spill. In conclusion, the Don Pedro oil spill induced an acute situation of oxidative stress on P. nobilis that were recovered twelve months later.

Polyphenols: well beyond the antioxidant capacity: polyphenol supplementation and exercise-induced oxidative stress and inflammation.

Moderate physical exercise leads the organism to adapt to this stressful situation. However, when exercise is exhaustive, it is also known to induce an overproduction of reactive species which can result in oxidative damage to macromolecules and tissues. Many studies have been carried out to evaluate the validity of dietary strategies or micronutrients in order to attenuate exercise-induced oxidative stress. Polyphenols are a large group of compounds widely distributed throughout the plant kingdom. This review summarizes recent evidence in relation to the effects of polyphenols as antioxidant and anti-inflammatory agents, using exercise as a model of study.

Biochemical responses of Mytilus galloprovincialis as biomarkers of acute environmental pollution caused by the Don Pedro oil spill (Eivissa Island, Spain).

In the present work, the potential use of several antioxidant and detoxification biomarkers in the digestive gland of wild mussels (Mytilus galloprovincialis) for biomonitoring the marine pollution induced by the Don Pedro oil spill has been investigated. Two locations from the East to South-East of Eivissa (Ibiza) and Formentera islands were selected, one extensively affected by the oil spill and the other one not affected and considered as the control area. Mussels were sampled one, two and six months after the Don Pedro accident. Polycyclic aromatic hydrocarbon (PAH) levels were significantly increased in the soft tissues of mussels in the affected area one month after the disaster, returning to normal values after six months. Markers of oxidative damage in lipids--malondialdehyde, and in proteins--carbonyl derivates, and antioxidant enzyme--catalase, superoxide dismutase and glutathione peroxidase, activities significantly increased as result of the spill oil after one month, returning to basal values at two month sampling time. Glutathione/glutathione disulfide ratio (GSH/GSSG), as a marker of the redox status, was reduced after one and two months indicating a more oxidized situation. Markers of detoxification--glutathione-S-transferase and cytochrome P4501A activities and metallothionein gene expression--were significantly increased by the oil spill one month after the accident, returning to the basal values at two month sampling time. In conclusion, the Don Pedro accident induced a transient situation of PAHs pollution resulting in enhanced antioxidant and detoxification defense systems in the wild mussel M. galloprovincialis returning to normal levels six months from the spill. The selected biomarkers are a useful tool for biomonitoring the response to acute exposure to pollutants in marine mussels.