Potential molecular mechanisms of myrtenal against colon cancer: A systematic review.

Colon cancer is a serious health problem across the globe with various dietary lifestyle modifications. It arises as an inflammation mediated crypts in the colon epithelial cells and undergoes uncontrolled cell division and proliferation. Bacterial enzymes contribute to a major outbreak in colon cancer development upon the release of toxic metabolites from the gut microflora. Pathogen associated molecular patterns and damage associated molecular patterns triggers the NLPR3 inflammasome pathways that releases pro-inflammatory cytokines to induce cancer of the colon. Contributing to this, specific chemokines and receptor complexes attribute to cellular proliferation and metastasis. Bacterial enzymes synergistically attack the colon mucosa and degenerate the cellular integrity causing lysosomal discharge. These factors further instigate the Tol like receptors (TLRs) and Nod like receptors (NLRs) to promote angiogenesis and supply nutrients for the cancer cells. Myrtenal, a monoterpene, is gaining more importance in recent times and it is being widely utilized against many diseases such as cancers, neurodegenerative diseases and diabetes. Based on the research data's, the reviews focus on the anticancer property of myrtenal by emphasizing its therapeutic properties which downregulate the inflammasome pathways and other signalling pathways. Combination therapy is gaining more importance as they can target every variant in the cellular stress condition. Clinical studies with compounds like myrtenal of the monoterpenes family is provided with positive results which might open an effective anticancer drug therapy. This review highlights myrtenal and its biological potency as a cost effective drug for prevention and treatment of colon cancer.

Anticancer Property of Digera muricata Leaf Extract: An In Vitro Study.

Aim The aim was to evaluate the anticancer potential of Digera muricata ethanolicleaf extract on MG-63 osteosarcoma cell lines. Materials and methods The anti-cancer properties of Digera muricata ethanolic leaf extract were evaluated on osteosarcoma cell lines using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the morphological changes in MG-63 cells were assessed after 24 hours using microscopic observation. Additionally, fluorescence microscopy was employed to evaluate the apoptotic changes after acridine orange/ethidium bromide (AO/EtBr) dual staining. Results The MTT assay revealed a dose-dependent cell death. The cell viability decreased with increase in concentrations of the extract, The cell viability was 89.98 ± 4.89 percentage at 25 µg/ml and 15.64 ± 3.64 percentage at 200 µg/ml concentrations. A concentartion of 116.95 µg/ml showed 50% inhibition (IC50). The morphological and dual staining studies also showed the extract's effectiveness in inducing apoptosis. Conclusion The ethanolic leaf extract of D. muricata could impart good antiproliferative activity in MG-63 cell lines. The extract could also induce apoptosis and hence, it may be considered as a potential anticancer agent for the development of drug formulation for the treatment of osteosarcoma.

Modulation of PPAR-γ, SREBP-1c and inflammatory mediators by luteolin ameliorates ß-cell dysfunction and renal damage in a rat model of type-2 diabetes mellitus.

BACKGROUND: Natural products have been recommended as a complementary therapy for type 2 diabetes mellitus (T2DM) due to constraints of safety and tolerability of existing anti-diabetic agents. Luteolin exhibits anti-diabetic and anti-inflammatory effects. Hence, the impact of luteolin on glucose homoeostasis and organ damage was investigated in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM in rats. METHODS AND RESULTS: Male Wistar rats were maintained on HFD (provided 55% energy as fat) for 10 days. Subsequently, a single dose of 40 mg/kg STZ was injected intraperitoneally on the 11th day. Seventy-two hours after STZ administration, diabetic rats with established hyperglycemia (fasting serum glucose > 200 mg/dL) were randomized into different groups having six rats each and orally administered either 0.5% hydroxy propyl cellulose or pioglitazone (10 mg/kg) or luteolin (50 mg/kg or 100 mg/kg) once daily for 28 days, while continuing HFD for respective groups. Luteolin significantly reduced hyperglycaemia, homoeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) levels, and improved hypoinsulinemia and HOMA of b-cell function (HOMA-B) in a dose-dependent manner. Increased TNF-α, IL-6 and NFκB levels in diabetic rats were significantly regulated. Additionally, luteolin significantly augmented PPAR-γ expression while attenuating sterol regulatory element binding protein-1c (SREBP-1c) expression. Histopathological scrutiny validated that luteolin effectively attenuated HFD-STZ-induced injury in pancreatic ß-cells and kidneys to near normalcy. CONCLUSION: Our study showed that luteolin ameliorated hyperglycemia and improved hypoinsulinemia, ß-cell dysfunction, and renal impairment in HFD-STZ-induced diabetic rats by attenuating inflammation and dysregulated cytokine secretion through modulation of PPAR-γ, TNF-α, IL-6 and NF-kB expression and down-regulation of SREBP-1c.

Recent trends in macromolecule-conjugated hybrid quantum dots for cancer theranostic applications.

Quantum dots (QDs) are small nanoparticles with semiconductor properties ranging from 2 to 10 nanometers comprising 10-50 atoms. The single wavelength excitation character of QDs makes it more significant, as it can excite multiple particles in a confined surface simultaneously by narrow emission. QDs are more photostable than traditional organic dyes; however, when injected into tissues, whole animals, or ionic solutions, there is a significant loss of fluorescence. HQD-based probes conjugated with cancer-specific ligands, antibodies, or peptides are used in clinical diagnosis. It is more precise and reliable than standard immunohistochemistry (IHC) at minimal protein expression levels. Advanced clinical studies use photodynamic therapy (PDT) with fluorescence imaging to effectively identify and treat cancer. Recent studies revealed that a combination of unique characteristics of QDs, including their fluorescence capacity and abnormal expression of miRNA in cancer cells, were used for the detection and monitoring progression of cancer. In this review, we have highlighted the unique properties of QDs and the theranostic behavior of various macromolecule-conjugated HQDs leading to cancer treatment.

Exosome Mediated Cancer Therapeutic Approach:Present Status and Future Prospectives.

The unique extracellular vesicles (EVs) or exosomes formed by the sequential invagination of the plasma membrane are diverse and encompass important constituents with biological functions. Speculations on its cell independent biological functions are significant and pose them as vital biomarkers and as drug delivery vehicles especially in cancer. EVs possess theragnostic values and are known to elicit specific immune response. Exosomes can also serve as potential nanocarriers for delivering miRNA, siRNA, anti-cancer drugs and membrane-associated proteins. Exosomes play a crucial role in regulating tumour progression, metastasis, and angiogenesis. This review thus portrays the multiple facets of exosomes, in concert with the source for exosomes production and further on its regulation and intercellular communication. The review also explores the recent advances, present status and the future prospective in the application of exosomes in cancer therapeutics and cancer diagnostics.

p-Coumaric Acid Nanoparticles Ameliorate Diabetic Nephropathy via Regulating mRNA Expression of KIM-1 and GLUT-2 in Streptozotocin-Induced Diabetic Rats.

Diabetic nephropathy (DN) has become a leading cause of end-stage renal failure worldwide. The goal of the current study was to examine the protective effects of chitosan-loaded p-Coumaric acid nanoparticles (PCNPs) in nephrotoxicity induced by streptozotocin (STZ). Because of the antidiabetic, anti-inflammatory, and antioxidant properties of PCNPs, the development of DN may be considerably decreased. In this study, the rats received a single intraperitoneal injection (i.p.) of STZ (45 mg/kg) to induce DN. PCNPs were given orally 80 mg/kg b.w to the rats for a duration of four weeks. Body weight, kidney weight, blood glucose, and insulin levels were measured at the end of the experiment. Serum and urine parameters were also examined, along with the histological, immunobiological, and tumor necrosis factor (TNF) and interleukin-6 (IL-6) expression of the nephrotic rats. To comprehend the impact of PCNPs, the expression patterns of the kidney injury molecule (KIM-1) and glucose transporter-2 (GLUT-2) were evaluated. Administration of PCNPs significantly increased body weight, decreased kidney weight and also ameliorated blood glucose levels in the nephropathic rats. The administration of PCNPs also reverted the levels of urea, serum creatinine, urinary NAG, ß-glucuronidase and albumin to near-normal levels. The administration of PCNPs also caused the levels of serum and urine parameters to return to near-normal levels. Additionally, the PCNP-treated rats had markedly reduced TNF-α, IL-6, and KIM-1 expressions as well as enhanced GLUT-2 mRNA expression. Our findings clearly showed that PCNP administration prevents the onset of DN in rats by lowering hyperglycemia, decreasing inflammation, and improving the expression of GLUT-2 mRNA in nephropathic rats.

Re-appraising the role of flavonols, flavones and flavonones on osteoblasts and osteoclasts- A review on its molecular mode of action.

Bone disorders have become a global concern illustrated with decreased bone mineral density and disruption in microarchitecture of natural bone tissue organization. Natural compounds that promote bone health by augmenting osteoblast functions and suppressing osteoclast functions has gained much attention and offer greater therapeutic value compared to conventional therapies. Amongst several plant-based molecules, flavonoids act as a major combatant in promoting bone health through their multi-faceted biological activities such as antioxidant, anti-inflammatory, and osteogenic properties. They protect bone loss by regulating the signalling cascades involved in osteoblast and osteoclast functions. Flavonoids augment osteoblastogenesis and inhibits osteoclastogenesis through their modulation of various signalling pathways. This review discusses the role of various flavonoids and their molecular mechanisms involved in maintaining bone health by regulating osteoblast and osteoclast functions.

Extracellular polymeric substances from marine actinobacterium of Micromonospora sp. and their antioxidant activity.

Actinobacteria, Gram-positive bacteria are the largest phyla among the major species in the bacteria domain. Micromonospora sp. is one of the secondary metabolite-producing Actinobacteria, and it has a comprehensive spectrum of antibacterial, antifungal, antitumor, antiviral, antiparasitic, diabetogenic anti-inflammatory, insecticidal, inhibitory of enzyme, antioxidant, and other biological activities. The objective of the study is to assess the antioxidant activity of the Actinobacterium Micromonospora sp. producing extracellular polymeric substances (EPSs). Enumeration and isolation of Actinobacteria from sediment samples are done. The marine Actinobacteria, Micromonospora sp. are identified by melanoid pigments and other chemotaxonomical characteristics. EPS is produced from the potential marine Actinobacteria and their components are estimated. The total antioxidant value is found for the EPS. The antioxidant activity of the ascorbic acid equivalent which was 142.65 µg/ml was equivalent to 150 µg/ml of the total antioxidant activity of the EPS produced. The role of different antioxidants and the action in different diseases were challenged since they could act as many mechanisms such as reducing power, providing hydrogen to radicals, and scavenging activity (free radical). To conclude, the potent antioxidant activity was obtained from Actinobacteria Micromonospora sp. producing extracellular substances. These extracts might bear anticancer metabolites and are considered a potent anticancer drug.

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management.

Diabetes is one of the most significant health issues across the world. People identified with diabetes are more vulnerable to various infections and are at a greater risk of developing cardiovascular diseases. The plant-based food we consume often contains many sterol-based bioactive compounds. It is well documented that these compounds could effectively manage the processes of insulin metabolism and cholesterol regulation. Insulin resistance followed by hyperglycemia often results in oxidative stress level enhancement and increased reactive oxygen species production. At the molecular level, these changes induce apoptosis in pancreatic cells and hence lead to insulin insufficiency. Studies have proved that plant sterols can lower inflammatory and oxidative stress damage connected with DNA repair mechanisms. The effective forms of phyto compounds are polyphenols, terpenoids, and thiols abundant in vegetables, fruits, nuts, and seeds. The available conventional drug-based therapies for the prevention and management of diabetes are time-consuming, costly, and with life-threatening side effects. Thereby, the therapeutic management of diabetes with plant sterols available in our daily diet is highly welcome as there are no side effects. This review intends to offer an overview of the present scenario of the anti-diabetic compounds from food ingredients towards the therapeutic beneficial against diabetes.

Molecular docking analysis of compounds from Andrographis paniculata with EGFR.

EGFR is linked with oral cancer. Therefore, it is of interest document the molecular docking analysis of compounds from Andrographis paniculata with EGFR. Data shows the binding features of five compounds 14- acetylandrographolide, andrograpanin, andrographolide, isoandrographolide and neoandrographolide from Andrographis paniculata with EGFR for further consideration.

Molecular docking analysis of stachydrine and sakuranetin with IL-6 and TNF-α in the context of inflammation.

Inflammation is a process triggered by pro-inflammatory cytokines and anti-inflammatory molecules. Therefore, it is of interest to document the anti-inflammatory activity of Stachydrine and Sakuranetin against the inflammatory target proteins IL-6 and TNF-α by using molecular docking analysis. Both compounds showed good binding features with the selected target proteins. Compared to Sakuranetin, the Stachydrine have low binding energy and good hydrogen bond interactions. Hence, data show that Stachydrine possessed high and specific inhibitory activity on tumor necrosis factor-α and interleukin-6.

Molecular docking analysis of capsaicin with apoptotic proteins.

Oral cancer is linked with apoptotic proteins such as Bcl-xl, Bcl-2 and Mcl-1. Therefore it is of interest to document the molecular docking analysis of capsaicin (principle present in the Capsicum annum) with apoptotic proteins in this context. We report the molecular binding features of capsaicin with apoptotic proteins such as Bcl-xl, Bcl-2 and Mcl-1 for further consideration.

ß-Sitosterol attenuates carbon tetrachloride-induced oxidative stress and chronic liver injury in rats.

Chronic liver diseases are clinically silent and responsible for significant morbidity and mortality worldwide. ß-Sitosterol (BSS), major phytosterol in plants, has a wide spectrum of protective effect against various chronic ailments. We investigated the hepatoprotective effect of BSS against carbon tetrachloride (CCl4)-induced chronic liver injury in rats. Thirty rats were divided into five groups, with six animals in each group. Group I rats served as control while groups II, III, IV, and V rats were injected intraperitoneally with CCl4 (0.2 mL/100 g b.w. in olive oil (1:1)) for 7 consecutive weeks. After 7 weeks, group II rats were left without any treatments and served as CCl4 alone group, while groups III, IV, and V rats were treated with BSS 25 and 50 mg/kg b.w. and silymarin 100 mg/kg b.w. as oral post-treatments respectively, for the next 4 weeks. At the end of the experiment, hepatotoxicity marker enzymes in serum, oxidative stress, and fibrosis marker were analyzed. CCl4 administration caused significant elevation of marker enzymes of hepatotoxicity in serum and increased lipid peroxidation and fibrosis markers such as hydroxyproline, collagen, α-smooth muscle actin, vimentin, desmin, and matrix metalloproteinases 9 in liver tissue of rats. This treatment also caused a significant diminution of intracellular enyzmic antioxidants such as SOD and CAT in the liver tissue of rats. All the above adversities were significantly mitigated by the BSS post-treatments. The results suggest that BSS could have a hepatoprotective effect against oxidative stress-mediated CLD induced by CCl4.