scholarly journals Protection from Metabolic Dysregulation, Obesity, and Atherosclerosis by Citrus Flavonoids: Activation of Hepatic PGC1α-Mediated Fatty Acid Oxidation

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Erin E. Mulvihill ◽  
Murray W. Huff
Keyword(s):  
Therapeutic Potential ◽  
Cardiovascular Complications ◽  
Therapeutic Agents ◽  
Metabolic Effects ◽  
Lipid Homeostasis ◽  
Acid Oxidation ◽  
Metabolic Dysregulation ◽  
Citrus Flavonoids ◽  
Molecular Studies ◽  
Metabolic Regulators

Studies in a multitude of models including cell culture, animal and clinical studies demonstrate that citrus-derived flavonoids have therapeutic potential to attenuate dyslipidemia, correct hyperinsulinemia and hyperglycemia, and reduce atherosclerosis. Emerging evidence suggests the metabolic regulators, PPARα and PGC1α, are targets of the citrus flavonoids, and their activation may be at least partially responsible for mediating their metabolic effects. Molecular studies will add significantly to the concept of these flavonoids as viable and promising therapeutic agents to treat the dysregulation of lipid homeostasis, metabolic disease, and its cardiovascular complications.

scholarly journals Flavonoids from the Genus Euphorbia: Isolation, Structure, Pharmacological Activities and Structure–Activity Relationships

2021 ◽  
Vol 14 (5) ◽  
pp. 428
Author(s):  
Douglas Kemboi Magozwi ◽  
Mmabatho Dinala ◽  
Nthabiseng Mokwana ◽  
Xavier Siwe-Noundou ◽  
Rui W. M. Krause ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Structure Activity Relationship ◽  
Biological Properties ◽  
Therapeutic Agents ◽  
Skeletal Structure ◽  
Activity Relationship ◽  
Hydroxyl Groups ◽  
Structure Activity ◽  
Review Reports

Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure–activity relationship of Euphorbia flavonoids for the period covering 2000–2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Of the investigated species, over 80 different types of flavonoids have been isolated to date. Most of the isolated flavonoids were flavonols and comprised simple O-substitution patterns, C-methylation and prenylation. Others had a glycoside, glycosidic linkages and a carbohydrate attached at either C-3 or C-7, and were designated as d-glucose, l-rhamnose or glucorhamnose. The structure–activity relationship studies showed that methylation of the hydroxyl groups on C-3 or C-7 reduces the activities while glycosylation loses the activity and that the parent skeletal structure is essential in retaining the activity. These constituents can therefore offer potential alternative scaffolds towards development of new Euphorbia-based therapeutic agents.

scholarly journals Chalepin and Chalepensin: Occurrence, Biosynthesis and Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1609
Author(s):  
Lutfun Nahar ◽  
Shaymaa Al-Majmaie ◽  
Afaf Al-Groshi ◽  
Azhar Rasul ◽  
Satyajit D. Sarker
Keyword(s):  
Medicinal Plant ◽  
Critical Appraisal ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
Review Article ◽  
Natural Distribution ◽  
Antiplatelet Aggregation ◽  
Ruta Chalepensis ◽  
The Family ◽  
Novel Therapeutic

Dihydrofuranocoumarin, chalepin (1) and furanocoumarin, chalepensin (2) are 3-prenylated bioactive coumarins, first isolated from the well-known medicinal plant Ruta chalepensis L. (Fam: Rutaceae) but also distributed in various species of the genera Boenminghausenia, Clausena and Ruta. The distribution of these compounds appears to be restricted to the plants of the family Rutaceae. To date, there have been a considerable number of bioactivity studies performed on coumarins 1 and 2, which include their anticancer, antidiabetic, antifertility, antimicrobial, antiplatelet aggregation, antiprotozoal, antiviral and calcium antagonistic properties. This review article presents a critical appraisal of publications on bioactivity of these 3-prenylated coumarins in the light of their feasibility as novel therapeutic agents and investigate their natural distribution in the plant kingdom, as well as a plausible biosynthetic route.

scholarly journals Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities

2021 ◽  
Author(s):  
Richard Radun ◽  
Michael Trauner
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Therapeutic Potential ◽  
Farnesoid X Receptor ◽  
Metabolic Homeostasis ◽  
Nonalcoholic Fatty Liver ◽  
Metabolic Dysregulation ◽  
Attractive Therapeutic Target

AbstractNonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, increasingly contributing to the burden of liver transplantation. In search for effective treatments, novel strategies addressing metabolic dysregulation, inflammation, and fibrosis are continuously emerging. Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.

scholarly journals Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Basma Basha ◽  
Samson Mathews Samuel ◽  
Chris R. Triggle ◽  
Hong Ding
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Endoplasmic Reticulum ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Therapeutic Agents ◽  
Recent Past

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

Secretin as a satiation whisperer with the potential to turn into an obesity-curbing knight

Endocrinology ◽  
2021 ◽  
Author(s):  
Katharina Schnabl ◽  
Yongguo Li ◽  
Mueez U-Din ◽  
Martin Klingenspor
Keyword(s):  
Bariatric Surgery ◽  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Weight Control ◽  
Therapeutic Potential ◽  
Physiological Mechanism ◽  
Gut Hormones ◽  
Metabolic Effects ◽  
Beneficial Effects

Abstract The obesity pandemic requires effective preventative and therapeutic intervention strategies. Successful and sustained obesity treatment is currently limited to bariatric surgery. Modulating the release of gut hormones is considered promising to mimic bariatric surgery with its beneficial effects on food intake, body weight and blood glucose levels. The gut peptide secretin was the first molecule to be termed a hormone; nevertheless, it only recently has been established as a legitimate anorexigenic peptide. In contrast to gut hormones that crosstalk with the brain either directly or by afferent neuronal projections, secretin mediates meal-associated brown fat thermogenesis to induce meal termination, thereby qualifying this physiological mechanism as an attractive, peripheral target for the treatment of obesity. In this perspective, it is of pivotal interest to deepen our yet superficial knowledge on the physiological roles of secretin as well as meal-associated thermogenesis in energy balance and body weight regulation. Of note, the emerging differences between meal-associated thermogenesis and cold-induced thermogenesis must be taken into account. In fact, there is no correlation between these two entities. In addition, the investigation of potential effects of secretin in hedonic-driven food intake, bariatric surgery as well as chronic treatment using suitable application strategies to overcome pharmacokinetic limitations will provide further insight into its potential to influence energy balance. The aim of this article is to review the facts on secretin’s metabolic effects, address prevailing gaps in our knowledge, and provide an overview on the opportunities and challenges of the therapeutic potential of secretin in body weight control.

Abstract 67: Intervention With Citrus Flavonoids Reverses Existing Metabolic Disorders and Attenuates the Progression of Advanced Atherosclerosis in High Fat--Fed LDLr-/- Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Amy C Burke ◽  
Brian G Sutherland ◽  
Cynthia G Sawyez ◽  
Dawn E Telford ◽  
Joseph Umoh ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Caloric Intake ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
High Fat ◽  
Rapid Weight Gain ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Citrus Flavonoids

Previous studies demonstrated that addition of the citrus flavonoids naringenin or nobiletin to a high-fat diet prevented the development of many disorders linked to the metabolic syndrome. In the present study, we assessed the ability of intervention with nobiletin or naringenin to reverse pre-established obesity, insulin resistance, hepatic steatosis, dyslipidemia and attenuate atherogenesis. Ldlr-/- mice were fed chow or a high-fat, cholesterol-containing (HFHC) diet for 12 weeks. For an additional 12 weeks, the HFHC-fed mice: (1) continued on the HFHC diet or were transferred to (2) chow, (3) HFHC + 3% naringenin, or (4) HFHC + 0.3% nobiletin. Following rapid weight gain during HFHC-induction, intervention with naringenin or nobiletin stimulated weight loss, while maintaining caloric intake. Micro-CT imaging revealed flavonoid intervention reversed adipose tissue accumulation by 40-60% in both subcutaneous and visceral depots. At 12 weeks, the HFHC-fed mice were hyperinsulinemic (6-fold), which was accompanied by increased fasting plasma glucose. Intervention with either flavonoid normalized plasma insulin and glucose and corrected impaired insulin and glucose tolerance. The HFHC diet increased cholesterol within VLDL (10-fold) and LDL (6-fold), which was reduced (~50%) by either naringenin or nobiletin intervention. HFHC-induction significantly increased hepatic steatosis. Flavonoid intervention reduced hepatic cholesterol (>50%) and triglyceride (~20%) via increased expression of Pgc1a and Cpt1a and reduced expression of Srebp1c. HFHC-induction increased atherosclerotic lesion area (13-fold), which was increased a further 2.5-fold at 24 weeks. Flavonoid intervention modestly retarded lesion size progression (16-20%). As well, intervention with naringenin or nobiletin slowed the accumulation of aortic cholesterol (~30-45%) and reduced lesional necrotic area (~25%), suggesting improved lesion morphology. These studies demonstrate in mice with pre-existing metabolic dysregulation and atherosclerosis that intervention with naringenin or nobiletin reverses obesity, dyslipidemia, hepatic steatosis and insulin resistance, and modestly attenuates the progression of advanced atherosclerosis.

scholarly journals Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4998
Author(s):  
Hitesh Chopra ◽  
Protity Shuvra Dey ◽  
Debashrita Das ◽  
Tanima Bhattacharya ◽  
Muddaser Shah ◽  
...  
Keyword(s):  
Drug Targets ◽  
Therapeutic Potential ◽  
Curcuma Longa ◽  
Therapeutic Agents ◽  
Target Specificity ◽  
Production Scale ◽  
Curcumin Nanoparticles ◽  
Active Moiety ◽  
Bioactive Component ◽  
Biological Studies

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level.

scholarly journals Neuroprotective Effects, Biological Activities and Therapeutic Potential of Phytochemicals: A Comprehensive Review

2020 ◽  
pp. 1-11
Author(s):  
Xi-jun Wang ◽  
Shi Qiu ◽  
Aihua Zhang ◽  
Jian-hua Miao ◽  
Hui Sun ◽  
...  
Keyword(s):  
Natural Products ◽  
Neurological Disorders ◽  
Chemical Biology ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Neuroprotective Effects ◽  
Alternative Medicines ◽  
Pharmacological Targets ◽  
The World

The incidence of neurological disorders is growing in the world together with an increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathology, which make necessary to search for new therapeutic agents. Natural products, most of them used in phytochemicals from herbal medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Numerous herbs have been applied to neurodegenerative disease treatments as complementary and alternative medicines. In the 21st century, omics-coupled functional pharmacology was developed for neurodegenerative drug discovery from natural products. In this article, we firstly provide the latest understanding of neurological disorders on risk factors, category, diagnosis and treatment, and then specially present an overview of natural products in neuroprotective effects research from chemical biology to pharmacological targets, and also discuss the natural products application and future challenge.

scholarly journals AMPK as a mediator of hormonal signalling

2009 ◽  
Vol 44 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Chung Thong Lim ◽  
Blerina Kola ◽  
Márta Korbonits
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Effects ◽  
Whole Body ◽  
Acid Oxidation ◽  
Treatment Of Obesity ◽  
Amp Activated Protein Kinase ◽  
Hormonal Signalling

AMP-activated protein kinase (AMPK) is a key molecular player in energy homeostasis at both cellular and whole-body levels. AMPK has been shown to mediate the metabolic effects of hormones such as leptin, ghrelin, adiponectin, glucocorticoids and insulin as well as cannabinoids. Generally, activated AMPK stimulates catabolic pathways (glycolysis, fatty acid oxidation and mitochondrial biogenesis) and inhibits anabolic pathways (gluconeogenesis, glycogen, fatty acid and protein synthesis), and has a direct appetite-regulating effect in the hypothalamus. Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders. Thus, AMPK is now recognised as a potential target for the treatment of obesity and associated co-morbidities.

Sign in / Sign up

Export Citation Format

Share Document