Phenolics Extracted from Jasminum sambac Mitigates Diabetic Cardiomyopathy by Modulating Oxidative Stress, Apoptotic Mediators and the Nfr-2/HO-1 Pathway in Alloxan-Induced Diabetic Rats.

Diabetes mellitus is a chronic metabolic disorder defined as hyperglycemia and pancreatic ß-cell deterioration, leading to other complications such as cardiomyopathy. The current study assessed the therapeutic effects of phenolic acids extracted from Jasminum sambac phenols of leaves (JSP) against diabetes-induced cardiomyopathy in rats. The rats were divided into four groups, with each group consisting of 20 rats. The rats were given intraperitoneal injections of alloxan monohydrate (150 mg/kg) to induce diabetes. The diabetes-induced groups (III and IV) received treatment for six weeks that included 250 and 500 mg/kg of JSP extract, respectively. In the treated rats, the results demonstrated that JSP extract restored fasting glucose, serum glucose, and hyperlipidemia. Alloxan induced cardiomyopathy, promoted oxidative stress, and altered cardiac function biomarkers, including cardiac troponin I, proBNP, CK-MB, LDH, and IMA. The JSP extract-treated rats showed improved cardiac function indicators, apoptosis, and oxidative stress. In diabetic rats, the mRNA expression of caspase-3, BAX, and Bcl-2 was significantly higher, while Bcl-2, Nrf-2, and HO-,1 was significantly lower. In the treated groups, the expression levels of the BAX, Nrf-2, HO-1, Caspase-3, and Bcl-2 genes were dramatically returned to normal level. According to our findings, the JSP extract prevented cardiomyopathy and heart failure in the hyperglycemic rats by improving cardiac biomarkers and lowering the levels of hyperlipidemia, oxidative stress, apoptosis, hyperglycemia, and hyperlipidemia.

Diverse Signaling Pathways and Current Status of Molecular Targeted Treatments for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of death associated with cancer. Various molecular mechanisms are involved in HCC development. Alterations in these molecular mechanisms include chromosomal instability, gene mutations, and variations in protein expressions. A number of cell signaling pathways that are associated with the occurrence of apoptosis, cell proliferation, and angiogenesis provide new prospects for the development of HCC treatments. Newly designed, potential therapeutic regimens target specific receptors, kinases, and vital proteins. Sorafenib is the only FDA-approved drug for HCC treatment, and it has been found that the complex genomic aberrations in HCC can be overcome using combination therapy. For example, therapeutic benefits have been gained using sorafenib with doxorubicin, oxaliplatin, cisplatin, and monoclonal antibodies. In addition, elumetinib, carbozantinib, and refametinib may be effective when used in combination with sorafenib. Drugs that target several signaling pathways have shown promising results in phase 3 clinical trials, and clinical studies using these drugs have changed the management strategy for HCC, particularly with the use of combination therapeutic regimens. Such research has improved the current standards of care and influenced clinical decision making.

Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats.

CONTEXT: Angelica sinensis L. (Umbelliferae) has medicinal properties. OBJECTIVES: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia. MATERIALS AND METHODS: Thirty healthy adult male albino rats were randomly divided into five groups (n = 6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20 mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100 IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1 g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1 g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. RESULTS: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0 g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm3), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2 pg/cell) values. In the group treated with ASP, the Hb (13.7 g/dL) and RBCs (7.8 million/mm3) increased significantly (p < 0.05). The combination of ASP and ACEI led to the significant (p < 0.05) reduction in Hb (10.7 g/dL), PCV (33.3%), RBCs (6.0 million/mm3), MCV (54.42 fL) and MCH (16.44 pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group. CONCLUSION: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.

Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice.

The present study was carried out to investigate the antiulcer activity of Berberis vulgaris (Zereshk) seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150 mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300 mg/kg, 600 mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced the tissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris (900 mg/kg) showed similar results as synthetic antiulcer drug omeprazole.

Antioxidant and Hepatoprotective Activities of Acacia jacquemontii Stem Extract against High-fat and CCl4-induced Liver Injury in Rat's Model.

BACKGROUND: Chronic liver injury leads to liver inflammation and fibrosis, activating myofibroblasts in the liver and secreting extracellular matrix proteins that make the fibrous scar. OBJECTIVES: The purpose of our study was to characterize the polyphenolic content present in Acacia jacquemontii stem and evaluate its antioxidant and hepatoprotective activity. METHODS: The phenolic contents in Acacia jacquemontii polyphenolic extract (AJPPE) were characterized using high-performance liquid chromatography (HPLC). The hepatoprotective and antioxidant activity of AJPPE were determined through biochemical parameters (ALT, AST, and ALP), lipid profile (TC, TG, HDL, and LDL), antioxidant biomarkers (SOD, LPO, GSH, and CAT), anti-fibrotic activity (collagen deposition), and histopathological analysis. RESULTS: HPLC analysis of AJPPE showed the presence of polyphenols, including chlorogenic acid, P-coumaric acid, caffeic acid, and kaempferol, in a remarkable therapeutic range. Results of the in vivo analysis showed a significant decrease in the level of lipid profile, including LDL (low-density lipoprotein), TC (total cholesterol), triglycerides, liver function markers (AST, ALT, and ALP), collagen deposition and significantly increased the level of anti-oxidative biomarkers (CAT, SOD, LPO, and GSH) by using AJPPE. CONCLUSION: The above-mentioned results have shown that AJPPE possesses significant antioxidative and hepatoprotective effects. Furthermore, histopathological results also supported the antioxidant and hepatoprotective potential of AJPPE.

Acacia jacquemontii ethyl acetate extract reduces hyperglycemia and pro-inflammatory markers while increasing endogenous antioxidant potential in alloxan-induced diabetic rats.

Acacia jacquemontii possess has numerous traditional therapeutic uses. The rationale of this study was to investigate the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in the downregulation of hyperglycemia. The current study was performed in two parts, in vitro, through characterization (high-performance liquid chromatography), estimation of total phenolic content, total flavonoid content, antioxidant (2,2-diphenyl-1-picrylhydrazylassay), and α-amylase inhibitory activities of the studied extract, and in vivo using Wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250 mg/kg, and AJEAE 500 mg/kg. The effects of AJEAE on fasting plasma glucose, plasma insulin, HOMA-IR, oral glucose tolerance test, glycated hemoglobin (HBA1c), lipid profile, inflammatory cytokines (Interleukin-6, tumor necrosis factor-alpha), and oxidative stress markers (lipid peroxidation, nitic oxide, superoxide dismutase, catalase, glutathione peroxidase) were evaluated. Our findings confirmed the presence of quercetin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinnamic acid, and ferulic acid in AJEAE. Total flavonoid and phenolic contents in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g, respectively. Significant inhibition of DPPH (69.470%/1 mg/ml) and α-amylase (71.8%/1 mg/ml) activities were exhibited by AJEAE. Alloxan-injected rats showed marked hyperglycemia and hypoinsulinemia, and increased inflammatory marker levels as compared to normal control (p < 0.001). Additionally, raised levels of triglyceride (139.7 ± 2.771), total cholesterol (198.7 ± 1.856), very low-density lipoprotein (33.43 ± 0.2728), low-density lipoprotein (155.5 ± 2.754), lipid peroxidation, and nitric oxide (p < 0.001) and decreased levels of high-density lipoprotein (17.20 ± 0.1732), superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic rats (p < 0.001). AJEAE significantly (p < 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic ß cells. Conclusively, our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and pancreatic beta ß cell regenerative properties of AJEAE against alloxan-induced diabetes.

Opuntia ficus indica (L.) fruit extract alleviates oxidative stress through activation of dual oxidases and Keap1/Nrf2 signaling cascades in high-fat-diet associated atherosclerosis rats.

Atherosclerosis is a metabolic disorder characterized by chronic inflammation associated with progressive thickening and hardening of the large to medium-sized arteries due to plaque formation. The study aims to evaluate the antioxidative, anti-inflammatory, and hypolipidemic efficacy of Opuntia ficus-indica (OFI) fruit extract against the high-fat-diet associated atherosclerotic rat model. In-vitro qualitative and quantitative phytochemical screening of OFI fruit extract revealed the significant presence of total phenolic content and total flavonoid contents. In-vitro antioxidant activity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl and FRAP assays that have shown their protective efficacy against the overproduction of reactive oxygen species. Results revealed that the level of total oxidant stress was significantly (P < 0.05) reduced and down expression levels of dual oxidases (Duox, Duoxa-1, and Duox-2) in all the treatment groups (I, II, III) as compared with positive control were observed. The total antioxidant capacity was significantly (P < 0.05) increased in all treatment groups in comparison with the positive control group and higher expression level of the Nrf-2 signaling pathway (Nfe-212, NFR-1, and Keap-1) was observed in all the treatment groups compared with the positive control group. Histopathological examination of the aorta showed that high-fat diet markedly increased endothelial lining and thickness of tunica media and adventitia, with irregular media segments having wavy laminae, and a significant increase in entropy of fibers disposition was observed. Conclusively, OFI fruit extract has shown promising protective, anti-oxidative, and anti-inflammatory efficacy through the restoration of normal parenchyma in high-fat dieting-associated oxidative stress and endothelial inflammation.

Gisekia pharnaceoides Restores Colonic Mucosal Homeostasis by Regulating Antioxidant Enzyme System and Cytokines Signaling in Ulcerative Colitis Mice Model.

BACKGROUND: Gisekia pharnaceoides Linn. (Aizoaceae), traditionally known as baluka saag or sareli is commonly found in the deep Cholistan region of Pakistan. It is used by the native community for the mitigation of a range of diseases, including inflammatory disorders and gastric ulcers. OBJECTIVE: This study is designed to evaluate the defensive impact of G. pharnaceoides in acetic acid-induced ulcerative colitis in mice and to discover the mechanism for anti-inflammatory action. METHODS: The ethanolic crude extract of G. pharnaceoides (Gp.Cr) was prepared and evaluated for phytochemical substances by preliminary screening and HPLC analysis. Anti-inflammatory activity of Gp.Cr (300 and 500 mg/kg) was examined by administration of 200 µl of 7.5% acetic acid intra- rectally to induce ulcerative colitis and colonic mucosal injury, while mucosal homeostasis was evaluated by disease activity index, colonic ulcer score, and hematological parameters. The anti-inflammatory potential was quantified by assessing antioxidant enzymes (SOD, CAT, GPX-1), lipid peroxides, nitric oxide, and cytokines (IL-1ß, IL-6, TNF-α) immunoassays and further analyzed by histological analysis of colon tissues. RESULTS: Phytochemical screening of Gp.Cr revealed the presence of alkaloids, phenols, flavonoids, steroids, tannins, and saponins, while HPLC analysis confirmed the presence of quercetin, gallic acid, coumaric and sinapic acid. In acetic acid-induced ulcerative colitis model, Gp.Cr (300 and 500 mg/kg) along with sulphasalazine (500 mg/kg) decreased disease activity index, ulcer scores, and hematological parameters. Gp.Cr showed a significant anti-inflammatory potential by increasing antioxidant enzymes and decreasing lipid peroxides, nitric oxide, and cytokines levels. Histopathological examination showed a significant decline in ulceration and tissue disruption. CONCLUSION: Hence, the findings confirmed the effectiveness of G. pharnaceoides crude extract in the treatment of ulcerative colitis and might be a promising remedy to manage inflammatory disorders.

Effect of Caesalpinia bonduc Polyphenol Extract on Alloxan-Induced Diabetic Rats in Attenuating Hyperglycemia by Upregulating Insulin Secretion and Inhibiting JNK Signaling Pathway.

Caesalpinia bonduc has been used in herbal medicines for the treatment of a wide range of diseases from decades. The present study has explored the remedial potential and underlying mechanism of polyphenol extract of Caesalpinia bonduc in alloxanized diabetic rats. HPLC/MS analysis confirmed the presence of phenolics in considerable concentrations in Caesalpinia bonduc extract. Administration of different doses (250 and 500 mg/kg) of CPP extract to hyperglycemic rats for 8 weeks restored blood and serum glucose, insulin, glycosylated hemoglobin, leptin, amylin, and carbohydrate metabolizing enzymes level towards normal compared to alloxanized diabetic group. The effect of CPP extract on various genes such as Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 in insulin signaling pathway and Traf-4, Traf-6, and Mapk-8 in MAPK downstream JNK cascade was examined through qRT-PCR to access the core molecular mechanism involved in CPP-induced recovery of diabetes. Results have revealed that CPP extract reduced oxidative stress in pancreatic ß cells by restoring free radical scavenging potential, reducing the mRNA expression of Mapk-8, Traf-4, and Traf-6, and increasing the Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 expression ensuing regeneration of ß cells and subsequent insulin release from pancreas. The results obtained in this study recommend that CPP extract may be a promising therapeutic restorative agent in the treatment of diabetes mellitus.

Gastric Carcinoma: Recent Trends in Diagnostic Biomarkers and Molecular Targeted Therapies.

Gastric cancer is generally associated with poor survival rates and accounts for a remarkable proportion of global cancer mortality. The prevalence of gastric carcinoma varies in different regions of world and across teh various ethnic groups. On the basis of pathological assessment, gastric cancer can be categorized as intestinal and diffuse carcinomas. The etiology is diverse, including chemical carcinogen exposure, and high salt intake Helicobacter pylori also plays a vital role in the pathogenesis of certain gastric carcinomas. The development of gastric cancer involves various alterations in mRNAs, genes (GOLPH3, MTA2) and proteins (Coronins). miRNAs, Hsamir135b, MiR21, miR106b, miR17, miR18a, MiR21, miR106b, miR17, miR18a and MiRNA375, miRNA1955p are the latest diagnostic biomarkers which can facilitate the early diagnosis of gastric carcinomas. Recent development in the treatment strategies for gastric carcinoma include the introduction of monoclonal antibodies, TKI inhibitors, inhibitors of PDGFR ß, VEGFR1, VEGFR2, AntiEGFR and antiHER2 agents which can be applied along with conventional therapies.

Breast cancer: major risk factors and recent developments in treatment.

Breast cancer is the most common in women worldwide, with some 5-10% of all cases due to inherited mutations of BRCA1 and BRCA2 genes. Obesity, hormone therapy and use of alcohol are possible causes and over-expression of leptin in adipose tissue may also play a role. Normally surgery, radiation therapy and chemotherapy allow a good prognosis where screening measures are in place. New hope in treatment measures include adjuvant therapy, neoadjuvant therapy, and introduction of mono-clonal antibodies and enzyme inhibitors.