Nanoformulations of natural products for management of metabolic syndrome.

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Pharmacological effects of gallic acid in health and diseases: A mechanistic review.

OBJECTIVES: Gallic acid is a natural phenolic compound found in several fruits and medicinal plants. It is reported to have several health-promoting effects. This review aims to summarize the pharmacological and biological activities of gallic acid in vitro and animal models to depict the pharmacological status of this compound for future studies. MATERIALS AND METHODS: All relevant papers in the English language were collected up to June 2018. The keywords of gallic acid, antioxidant, anticancer, antimicrobial, gastrointestinal-, cardiovascular-, metabolic-, neuropsychological-, and miscellaneous- diseases were searched in Google Scholar, PubMed, and Scopus. RESULTS: Several beneficial effects are reported for gallic acid, including antioxidant, anti-inflammatory, and antineoplastic properties. This compound has been reported to have therapeutic activities in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders. CONCLUSION: Current evidence confirms the pharmacological and therapeutic interventions of gallic acid in multiple health complications; however, available data are limited to just cellular and animal studies. Future investigations are essential to further define the safety and therapeutic efficacy of gallic acid in humans.

Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies.

Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti-inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.

Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications.

Diabetes affects a large population of the world. Lifestyle, obesity, dietary habits, and genetic factors contribute to this metabolic disease. A target pathway to control diabetes is the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is a heterotrimeric protein with α, ß, and γ subunits. In several studies, AMPK activation enhanced glucose uptake into cells and inhibited intracellular glucose production. Impairment of AMPK activity is present in diabetes, according to some studies. Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK. Thus, drugs that activate and regulate AMPK are potential candidates for the treatment of diabetes. In addition, many patients encounter important adverse effects, like hypoglycemia, while using allopathic drugs. As a result, the investigation of plant-derived natural drugs that lack adverse side effects and treat diabetes is necessary. Natural products like berberine, quercetin, resveratrol, and so forth have shown significant potential in regulating and activating the AMPK pathway which can lead to manage diabetes mellitus and its complications.

Medicinal plants and their isolated phytochemicals for the management of chemotherapy-induced neuropathy: therapeutic targets and clinical perspective.

BACKGROUND: Chemotherapy, as one of the main approaches of cancer treatment, is accompanied with several adverse effects, including chemotherapy-induced peripheral neuropathy (CIPN). Since current methods to control the condition are not completely effective, new treatment options should be introduced. Medicinal plants can be suitable candidates to be assessed regarding their effects in CIPN. Current paper reviews the available preclinical and clinical studies on the efficacy of herbal medicines in CIPN. METHODS: Electronic databases including PubMed, Scopus, and Cochrane library were searched with the keywords "neuropathy" in the title/abstract and "plant", "extract", or "herb" in the whole text. Data were collected from inception until April 2018. RESULTS: Plants such as chamomile (Matricaria chamomilla L.), sage (Salvia officinalis L.), cinnamon (Cinnamomum cassia (L.) D. Don), and sweet flag (Acorus calamus L.) as well as phytochemicals like matrine, curcumin, and thioctic acid have demonstrated beneficial effects in animal models of CIPN via prevention of axonal degeneration, decrease in total calcium level, improvement of endogenous antioxidant defense mechanisms such as superoxide dismutase and reduced glutathione, and regulation of neural cell apoptosis, nuclear factor-ĸB, cyclooxygenase-2, and nitric oxide signaling. Also, five clinical trials have evaluated the effect of herbal products in patients with CIPN. CONCLUSIONS: There are currently limited clinical evidence on medicinal plants for CIPN which shows the necessity of future mechanistic studies, as well as well-designed clinical trial for further confirmation of the safety and efficacy of herbal medicines in CIPN. Graphical abstract Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction.

An update on dietary consideration in inflammatory bowel disease: anthocyanins and more.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder. A wealth of data pointed out that various aspects of chronic inflammation may be affected by several specific dietary factors. This paper calls attention to anthocyanins enriched plant food and anthocyanin dietary supplements, whose role in the management of IBD and its associated oncogenesis deems crucial. Area covered: We updated the most relevant dietary anthocyanins with potential anti-colitis and preventive effect on inflammatory associated colorectal cancer based on the recent animal and human researches along with revealing the major cellular and molecular mechanisms of action. Mounting evidence reported that anthocyanins enriched plant foods perform their protective role on IBD and inflammatory-induced colorectal cancer via different cellular transduction signaling pathways, including inflammatory transcription factors, SAPK/JNK and p38 MAPK cascade, JAK/STAT signaling, NF-kB/pERK/MAPK, Wnt signaling pathway, Nrf2 cytoprotective pathway as well as AMPK pathway and autophagy. Expert commentary: Combination of anthocyanins enriched dietary supplements with existing medications can provide new therapeutic options for IBD patients. Further, well-designed randomized control trials (RCTs) are essential to evaluate the role of anthocyanins enriched medicinal foods as well as isolated anthocyanin components as promising preventive and therapeutic dietary agents for IBD and its associated oncogenesis.

Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective.

Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.

Naringenin and its Nano-formulations for Fatty Liver: Cellular Modes of Action and Clinical Perspective.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease mainly caused by high-fat diets and sudden feed changes, vitamin and energy deficiency, and inflammatory processes. Fatty liver leads to cirrhosis, hepatocellular carcinoma as well as liver failure. Lifestyle-modifying such as weight loss and a healthy diet have an inverse correlation with the risk of fatty liver. The promising effect of a diet rich in vegetables and fruits against fatty liver has been evidenced by several empirical studies focused on flavonoids. Among naturally occurring flavonoids, naringenin is one of the most important flavonoids which can be isolated from some edible fruits, especially citrus species. METHODS: In the present review, we discuss the effects of naringenin and its nano-formulations against fatty liver disease and the proposed molecular mechanism of action. A large number of studies attributed to naringenin anti-inflammatory, antioxidant and insulin-like actions, as well as different types of effects on sex hormone metabolism and lipid metabolism. Naringenin-loaded nanoparticles have been used to solve the limited stability, solubility, bioavailability and pharmacological activity of naringenin and, consequently, to improve its therapeutic effects. RESULTS AND DISCUSSION: Naringenin exerts diverse biological actions including the decrease of biomarkers of lipid peroxidation and protein carbonylation, increase of antioxidant defenses, scavenging of reactive oxygen species and modulation of signaling pathways related to fatty acid metabolism which can favor the oxidation of fatty acid, lower lipid accumulation in the liver and thereby prevent fatty liver.