Insulin-like growth factor-1 (IGF-1), a pleiotropic polypeptide, plays an essential role in CNS development and maturation. Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone that ...regulates blood glucose levels and fatty acid oxidation in the brain. GLP-1 also exhibits similar functions and growth factor-like properties to IGF-1, which is likely how it exerts its neuroprotective effects. Recent preclinical and clinical evidence indicate that IGF-1 and GLP-1, apart from regulating growth and development, prevent neuronal death mediated by amyloidogenesis, cerebral glucose deprivation, neuroinflammation and apoptosis through modulation of PI3/Akt kinase, mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK/ERK). IGF-1 resistance and GLP-1 deficiency impair protective cellular signaling mechanisms, contributing to the progression of neurodegenerative diseases. Over the past decades, IGF-1 and GLP-1 have emerged as an essential component of the neuronal system and as potential therapeutic targets for several neurodegenerative and neuropsychiatric dysfunctions. There is substantial evidence that IGF-1 and GLP-1 analogues penetrate the blood-brain barrier (BBB) and exhibit neuroprotective functions, including synaptic formation, neuronal plasticity, protein synthesis, and autophagy. Conclusively, this review represents the therapeutic potential of IGF-1 and GLP-1 signaling target activators in ameliorating neurological disorders.
Display omitted
•IGF-1 and GLP-1 signaling promotes neuronal cell proliferation, growth and CNS development.•Dysregulation of IGF-1 and GLP-1 involves in the progression of neurodegenerative and neuropsychiatric disorders.•IGF-1 and GLP-1 downregulation is associated with amyloidogenesis, cerebral glucose deprivation, neuroinflammation and apoptosis.•Potential IGF-1 and GLP-1 activators exhibit neuroprotective effects in various neurological dysfunctions.
Colon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA) is a natural and major pentacyclic triterpenoid ...glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions i.e., aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
Animals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks.
GA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin.
Our findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.
Arsenic, a group 1 carcinogen for humans, is abundant as compared to other trace elements in the environment and is present mainly in the Earth’s crust and soil. The arsenic distributions in ...different geographical regions are dependent on their geological histories. Anthropogenic activities also contribute significantly to arsenic release into the environment. Arsenic presents several complications to humans, animals, and plants. The physiology of plants and their growth and development are affected by arsenic. Arsenic is known to cause cancer and several types of organ toxicity, such as cardiotoxicity, nephrotoxicity, and hepatotoxicity. In the environment, arsenic exists in variable forms both as inorganic and organic species. From arsenic containing compartments, plants can absorb and accumulate arsenic. Crops grown on these contaminated soils pose several-fold higher toxicity to humans compared with drinking water if arsenic enters the food chain. Information regarding arsenic transfer at different trophic levels in food chains has not been summarized until now. The present review focuses on the food chain perspective of arsenic, which affects all components of the food chain during its course. The circumstances that facilitate arsenic accumulation in flora and fauna, as components of the food chain, are outlined in this review.
Display omitted
•Arsenic a non-essential metalloid is a serious threat to all organisms.•Arsenic a common contaminant in the food chain is transferred from soil-plant-food.•Arsenic bioaccumulation in the food chain is hazardous at all trophic levels.•Regulations to control arsenic exposure must be formulated to reduce contamination.
Display omitted
Cancer remains the topmost disorder of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the ...largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.
Neurodegenerative diseases (NDs) such as Alzheimer disease (AD), Parkinson disease (PD), and Huntington disease (HD) represent a major socio-economic challenge in view of their high prevalence yet ...poor treatment outcomes affecting quality of life. The major challenge in drug development for these NDs is insufficient clarity about the mechanisms involved in pathogenesis and pathophysiology. Mitochondrial dysfunction, oxidative stress and inflammation are common pathways that are linked to neuronal abnormalities and initiation of these diseases. Thus, elucidating the shared initial molecular and cellular mechanisms is crucial for recognizing novel remedial targets, and developing therapeutics to impede or stop disease progression. In this context, use of multifunctional compounds at early stages of disease development unclogs new avenues as it acts on act on multiple targets in comparison to single target concept. In this review, we summarize overview of the major findings and advancements in recent years focusing on shared mechanisms for better understanding might become beneficial in searching more potent pharmacological interventions thereby reducing the onset or severity of various NDs.
Nature has bestowed mankind with surplus resources (natural products) on land and
water. Natural products have a significant role in the prevention of disease and boosting of health in
humans and ...animals. These natural products have been experimentally documented to possess various
biological properties such as antioxidant, anti-inflammatory and anti-apoptotic activities. In
vitro and in vivo studies have further established the usefulness of natural products in various preclinical
models of neurodegenerative disorders. Natural products include phytoconstituents, like
polyphenolic antioxidants, found in herbs, fruits, nuts, vegetables and also in marine and freshwater
flora. These phytoconstituents may potentially suppress neurodegeneration and improve memory as
well as cognitive functions of the brain. Also, they are known to play a pivotal role in the prevention
and cure of different neurodegenerative diseases, such as Alzheimer’s disease, epilepsy, Parkinson’s
disease and other neuronal disorders. The large-scale neuro-pharmacological activities of
natural products have been documented due to the result of either the inhibition of inflammatory
processes, or the up-regulation of various cell survival proteins or a combination of both. Due to the
scarcity of human studies on neuroprotective effects of natural products, this review focuses on the
various established activities of natural products in in vitro and in vivo preclinical models, and their
potential neuro-therapeutic applications using the available knowledge in the literature.
In the present investigation, the ultrasound-assisted extraction (UAE) conditions and optimization of Rhododendron arboreum polysaccharide (RAP) yield were studied by a Box-Behnken response surface ...design and the evaluation of its antioxidant potential. Three parameters that affect the productivity of UAE, such as extraction temperature (50-90 °C), extraction time (10-30 min), and solid-liquid ratio (1-2 g/mL), were examined to optimize the yield of the polysaccharide percentage. The chromatographic analysis revealed that the composition of monosaccharides was found to be glucose, galactose, mannose, arabinose, and fucose. The data were fitted to polynomial response models, applying multiple regression analysis with a high coefficient of determination value (R
= 0.999). The data exhibited that the extraction parameters have significant effects on the extraction yield of polysaccharide percentage. Derringer's desirability prediction tool was attained under the optimal extraction conditions (extraction temperature 66.75 °C, extraction time 19.72 min, and liquid-solid ratio 1.66 mL/g) with a desirability value of 1 yielded the highest polysaccharide percentage (11.56%), which was confirmed through validation experiments. An average of 11.09 ± 1.65% of polysaccharide yield was obtained in optimized extraction conditions with a 95.43% validity. The in vitro antioxidant effect of polysaccharides of R. arboreum was studied. The results showed that the RAP extract exhibited a strong potential against free radical damage.
Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, ...seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while.
Colon cancer is the major health disease related with high mortality. Glycyrrhizic acid (GA) is an active constituent of licorice with anti-inflammatory and anticarcinogenesis effects. We ...investigated the chemopreventive potential of GA against 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis in Wistar rats.
Glycyrrhizic acid was administered orally at the dose of 15 mg/kg b.wt. and DMH was administered at the dose of 20 mg/kg b.wt. once a week for first 15 weeks. All the rats were euthanized after 30 weeks. GA supplementation significantly inhibited the tumor incidence and multiplicity.
Glycyrrhizic acid treatment reduced the expression of Ki-67, proliferating cell nuclear antigen (PCNA), nuclear factor-kappa B (NF-kB), cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) while enhanced the expression of p53, connexin-43, b-cell lymphoma-2 (Bcl-2), survivin, and cleaved caspase-3. Glycyrrhizic acid also significantly ameliorated DMH-induced decreased activities of caspase-9 and caspase-3. Furthermore, GA treatment reduced mast cells infiltration, attenuated the shifting of sialomucin to sulphomucin as well the levels of pro-inflammatory cytokines.
The findings of the study suggest that GA has chemopreventive potential against DMH-induced colon tumorigenesis plausibly through the attenuation of hyperproliferative responses, pro-inflammatory cytokines level, inflammatory and angiogenic markers, and apoptotic responses.
PDF
