Search

Hyperglycemia, hyperlipidemia, and atherosclerotic lesions may cause inflammation, which leads to chemokine production and changes in vascular responses. Hyperglycemia can impair normal protein folding by producing reactive oxygen species (ROS) and interacting with various signaling molecules, resulting in the activation of ER stress responses, that stimulates NF-kB, which regulates the expression of numerous genes involved in inflammation and vascular remodeling. Our previous studies have shown that diosgenin has a protective effect against streptozotocin (STZ) - induced oxidative damage in rat aorta. However, the therapeutic role of diosgenin on iRhom2/TACE signaling which has primarily been linked to the endoplasmic reticulum (ER)-stress induced inflammation is unknown. Diosgenin was administered (40 mg/kg b. wt, orally, for 4 weeks) to STZ-induced male albino rats. Fasting plasma glucose, blood pressure, nitrite level, lipid profile, and lipoprotein were assessed. Serum insulin and pro-inflammatory markers were analyzed using ELISA, mRNA and protein expression of iRhom2/TACE signaling molecules were analyzed using RT-PCR and western blotting analysis respectively. In silico study was also performed to find out the possible binding affinity of diosgenin with the ER stress signaling molecules. Through regulation of the iRhom2/TACE signaling molecules, diosgenin lowered dyslipidemia, hypertension, and pro-inflammatory cytokines (TNF-α, IL-1, IL-6, and IL-4) in the aorta of STZ induced diabetic rats. Results of molecular docking analysis also confirmed the potential binding interaction with iRhom2/TACE and TNF- α. These in silico and in vivo results indicated that a change in lipid profile and hypertension led to diabetes-related inflammation by promoting ER stress and, as a result, accelerating the aorta by generating proinflammatory cytokines and lipid deposition. This study concludes that diosgenin attenuates ER stress-induced inflammation in diabetic rat aorta by modulating the expression of pro-inflammatory, iRhom2/TACE mediated mechanism and hence diosgenin can be a therapeutic drug for the treatment of diabetes-induced inflammation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator-activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.

Cancer of lung is the utmost typical cause of death and the number of cases is increasing rapidly, which has emerged as a major leading health problem. A large amount of reports suggested that Benzo(a)pyrene [B(a)P] in cigarette smoke plays the major function in an initiation of cancer of lung. Cancer prevention or chemoprevention has become a compelling approach recently for treatment of lung cancer. So, discovering a fresh candidate with reduced toxicity for targeting lung cancer is vital and urgent. Sinapic acid which is a widely extracted in various vegetables and fruit exhibits rich anti-oxidant content, anti-inflammatory and anti-tumor activity. But, the chemopreventive action of sinapic acid against lung cancer initiated by B[a]P remain unclear. Following, an in-vivo B[a]P-stimulated lung cancer in swiss albino mice and an in-vitro human lung cancer cell (A549) model were established to examine the chemopreventive activities of sinapic acid. The levels of immunoglobulins (IgG and IgM), oxidative and inflammatory markers, and tumor markers level was studied using kits and standard methods. The results showed administration of sinapic acid ameliorates the exposure of B[a]P mediated lung cancer in swiss albino mice by a decline in IgG and IgM level, leukocyte count, neutrophil function tests, soluble immune complex, lipid peroxidation, pro-inflammatory cytokines, tumor markers (AHH, LDH, GGT, 5′NT and CEA) and enhanced phagocytic index, activity index and antioxidant defense enzymes. In addition, in-vitro studies showed potential cytotoxicity against human lung cancer and exhibited a potential cytotoxic (MTT assay) and apoptotic activity by elevation of ROS production and caspase activity (caspase-3 and caspase-9). Collectively, the results, clearly specifies sinapic acid can be utilized as an effective chemo preventative agent against lung carcinogenesis. [ABSTRACT FROM AUTHOR]

This work focuses on evaluating the therapeutic ability of betalain and its causal mechanisms in NSCLC both in vivo and in vitro. The experimental results demonstrated that betalain was able to reduce the viability of A549 cells dose dependently with undetectable toxicity toward normal human cells. Betalain also augmented the apoptotic cells of A549 and cell cycle arrest which was evidenced via increased in level of p53/p21 and decreasing levels of cyclin‐D1 complex. Moreover, betalain also reduced the levels of p‐PI3K, p‐Akt, and mammalian target of rapamycin significantly, justifying the pro‐apoptotic effect on A549 cells. The in vivo anticancer activity of betalain was determined further in nude mice injected with A549 cells. Xenograft in vivo experiments confirmed betalain administration of ameliorates the expression of pro‐inflammatory cytokines, tumor markers with reduced toxic effect. Accordingly, this combined study provides significant insight on betalain as a therapeutic agent. [ABSTRACT FROM AUTHOR]

The untreated systemic chronic inflammation leads to autoimmune diseases, hyperglycemia, cardiovascular diseases, type 2 diabetes, hypertension, osteoporosis, and so on. Phytochemicals effectively inhibit the inflammation, and numerous studies have proved that the phytocomponents possess anti‐inflammatory property via inhibiting the cyclooxygenase and lipoxygenase signaling pathways. Rhaponticin is one such phytochemical obtained from the perennial plant Rheum rhaponticum L. belonging to Polygonaceae family. We assessed the anti‐inflammatory potency of rhaponticin in endothelial cells induced with lipopolysaccharides (LPS). Four different endothelial cells induced with LPS were treated with rhaponticin and assessed for the nitric oxide generation. The cytotoxic potency of rhaponticin was evaluated in endothelial cells using the 3‐(4,5‐dimethylthizaol‐2yl)−2,5‐diphenyl tetrazolium bromide assay. The tumor necrosis factor‐α (TNF‐α) synthesis was quantified using the commercially available assay kit. The inflammatory signaling protein gene expression of TNF‐α, inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX2), and interleukin‐1β (IL‐1β) was analyzed with quantitative polymerase chain reaction (PCR) analysis. The gene expression of NADPH oxidase (NOX) cytoplasmic catalytic subunits gp91phox, p47phox, and p22phox was assessed with real‐time PCR analysis. Finally, to confirm the anti‐inflammatory potency of rhaponticin, the nuclear factor kappa B (NFκB) and mitogen‐activated protein kinase (MAPK) signaling protein expression was analyzed with immunoblotting analysis. Rhaponticin treatment significantly decreased the levels of nitric oxide and TNF‐α synthesis in LPS‐induced endothelial cells. It significantly decreased the gene expression of inflammatory proteins and NOX signaling protein. The protein expression of NFκB and MAPK signaling proteins was drastically decreased in rhaponticin‐treated endothelial cells induced with LPS. Overall, our results confirm that rhaponticin effectively inhibited the inflammation triggered by LPS in endothelial cells via downregulating iNOS, COX2, and NFκB and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a frequently diagnosed cancer that primarily affects the digestive system and an imperative cause of mortalities worldwide. In this work, we formulated the Tin oxide-Sodium alginate-Polyethylene glycol-Allyl isothiocyanate nanocomposites (SAP-Ally-NCs) and investigated its anticancer role against the DMH-provoked CRC in rats. The formulated SAP-Ally-NCs were characterized different techniques. The CRC was provoked to the rats via injecting 20 mg/kg of DMH and then administered with the formulated SAP-Ally-NCs for 16 weeks. The bodyweight changes and the polyp's incidences were detected and tabulated. The status of lipid peroxidation and antioxidant enzymes were studied by standard techniques. The inflammatory markers and xenobiotic enzymes level was scrutinized using respective kits. The mRNA expressions of various signaling molecules were examined by RT-PCR. The liver and colon tissues were examined microscopically to detect the histological changes. The formulated SAP-Ally-NCs treatment appreciably improved the body weight gain and suppressed the polyp's incidences in the DMH-challenged animals. SAP-Ally-NCs treated animals were demonstrated the notable reduction in the lipid peroxidation and inflammatory cytokines and elevated the antioxidant enzymes i.e. CAT and SOD activity. SAP-Ally-NCs administered animals exhibited the noticeable reduction in the expression of PCNA, cyclin-D1, iNOS, and COX-2 in the colon tissues. The histological findings also unveiled the therapeutic role of SAP-Ally-NCs. In conclusion, the SAP-Ally-NCs demonstrated the potent anticancer action against the DMH-provoked CRC in rats. In future, it could be a potent chemotherapeutic agent to the CRC. [ABSTRACT FROM AUTHOR]

Background: One of most abundant antioxidative component of vegetable oil and other plants, ß-sitosterol (SIT), is a highly effective antidiabetic drug. Our previous studies have shown that ß-sitosterol significantly improved glycaemic control in skeletal muscle and adipose tissue by facilitating insulin metabolic signalling molecules but its effects on the kidney is not known. Aim: The current study sought to determine whether SIT could also exert anti-diabetic effects by regulating insulin signalling and preventing inflammation the kidney, which is a major contributor to insulin resistance and diabetic nephropathy. To achieve this, adult male albino rats weredivided in to four groups. Group-1: control; Group 2; high fat diet-induced type-2 diabetic rats; Group 3: Diabetic rats treated with ß-sitosterol (20mg/kg b. wt, orally for 30 days) and group-4: Type-2 diabetic rats treated with metformin (50mg/kg.b. wt, orally for 30 days). Methods: Insulin receptor (IR), insulin receptor substrate-2 (IRS-2), Akt and interleukin -6 (IL-6), and kidney injury molecules mRNA (KIM-1) were analysed by Real Time-PCR analysis using gene specific primers. Results: mRNA expression of insulin signalling molecules (IR/IRS-1/Akt) were significantly improved in diabetic animals treated with 20mg dose of ß-sitosterol (p<0.05). Conversely, it reduced the mRNA levels of pro inflammatory signalling (IL-6) and gene involved in tissue remodelling (KIM-1) effectively (p<0.05). Conclusion:Our present findings for the first time clearly indicate that ß-sitosterol attenuates insulin resistance in the kidney by modulating the expression of proinflamamtion and KIM-1. Therefore, ß-sitosterol could be considered as a potential therapeutic natural drug candidate for the treatment of diabetic nephropathy and associated complications. [ABSTRACT FROM AUTHOR]

Disclosure of ultraviolet (UV) radiation is the key feature from environment to cause redness of the skin, inflammation, photoaging and skin cancer. 6-Shogaol, a spicy compound secluded from ginger, which shows anti-inflammatory effects. Present study was demonstrated the role of 6-Shogaol on UVB induced oxidative stress and photoaging signaling in human epidermal keratinocytes (HaCaT cells). In this study, UVB-irratiation (180 mJ/cm2) significantly elevated the intracellular ROS levels, depletion of antioxidants resulted in apoptotic HaCaT cells. MAPKs signaling are concerned in oxidative stress; these signaling events are measured as differentiation. We found that 6-shogaol prevents over expression of MAPKs (ERK1, JNK1 & p38), in disclosure of UVB in HaCaT cells. Moreover, 6-shogaol infringed Bax and Bcl-2 in which 20 μg 6-shogaol influenced apoptosis in HaCaT cells by investigating augmented appearance of Bax and condensed appearance of Bcl-2 in contrast to control HaCaT cells. These results suggest that 6-shogaol could be a successful healing agent provides fortification against UVB-induced provocative and oxidative skin reimbursement. • Disclosure of ultraviolet radiation is the key feature from environment to cause inflammation and photoaging. • 6-shogaol repressed the UVB induced inflammation retortion which includes the improved appearance of iNOS, COX-2, and TNF-α. • 6-shogaol might be an effectual defensive and healing agent shielding against UVB induced skin reimbursement. [ABSTRACT FROM AUTHOR]