The anti-toxic effect of the date palm fruit extract loaded on chitosan nanoparticles against CCl4-induced liver fibrosis in a mouse model.

The liver is the most important organ in the body. Hepatocyte oxidative damage occurs to excess ROS. Liver fibrosis is a mechanism that the immune system uses to treat extreme inflammation by repairing damaged tissue with the creation of a scar. The outcome of fibrosis may be reversed by consuming natural plant extracts with high ROS-scavenging ability. The date palm fruits contain caffeic acid, gallic acid, syringic acid, and ferulic acid, which have anti-inflammatory, antioxidant, and hepatoprotective properties. This study aimed to prepare a date fruit extract, load it onto chitosan nanoparticles, and compare its anti-fibrotic activity with the unloaded crude extract in the CCl4-mouse model. Our findings show that nanocomposite (Cs@FA/DEx) has anti-fibrotic properties and can improve liver function enzymes and endogenous antioxidant enzymes by inhibiting cell apoptosis caused by CCl4-induction in mice. Furthermore, significantly reduced CD95 and ICAM1 levels and down-regulation of TGFß-1 and collagen-α-1 expression demonstrated the anti-fibrotic effects of the Cs@FA/DEx. Therefore, the Cs@FA/DEx might be an innovative supplement for inhibiting liver fibrosis and hepatocyte inflammation induced by chemical toxins. Besides, this nano-supplement could be a promising anti-hepatocellular carcinoma agent as it has potent in vitro anticancer activity against the HePG2 cell line.

Avocado peel extract loaded on chitosan nanoparticles alleviates urethane toxicity that causes lung cancer in a mouse model.

Lung cancer progresses without obvious symptoms and is detected in most patients at late stages, causing a high rate of mortality. Avocado peels (AVP) were thought to be biowaste, but they have antioxidant and anticancer properties in vitro. Chitosan nanoparticles (Cs-NPs) were loaded with various plant extracts, increasing their in vitro and in vivo anticancer activities. Our goal was to load AVP onto Cs-NPs and determine the role of AVP-extract or AVP-loaded Cs-NPs in controlling the progression of lung cancer caused by urethane toxicity. The AVP-loaded chitosan nano-combination (Cs@AVP NC) was synthesized and characterized. Our in vitro results show that Cs@AVP NC has higher anticancer activity than AVP against three human cancer cell lines. The in vivo study proved the activation of apoptosis in lung cancer cells with the Cs@AVP NC oral treatment more than the AVP treatment. Additionally, Cs@AVP NC-treated animals showed significantly higher p53 and Bax-expression levels and lower NF-κB p65 levels in their lung tissues than in positive control animals. In conclusion, our study demonstrated the superior anticancer potency of Cs@AVP NC over AVP extract and its ability to inhibit lung cancer proliferation. Therefore, oral consumption of Cs@AVP NC might be a promising treatment for lung cancer.

Paullinia cupana seed extract ameliorated methotrexate-induced testicular dysfunction through the regulation of antioxidants, inflammatory, apoptosis/anti-apoptosis, and steroidogenesis-associated genes.

Methotrexate (MXT) is a medication used for cancer and rheumatoid treatment with severe organs toxicity as a side effect. Paullinia cupana (Guarana) is a plant with pleiotropic functions used to overcome the side effects of some chemotherapeutic medications. Current study aimed to examine the possible protective effect of guarana against oxidative stress induced by a single dose of MTX in testis. Forty male mice were divided into 4 groups (8 weeks old; 30 g weight), 1st group is negative control. The 2nd group is positive intoxicated group, received a single dose of MTX intraperitoneally (IP; 20 mg/kg BW in saline) on day 7. The 3rd group received guarana seed extract orally (300 mg/kg BW daily) for 12 days. The protective group was given guarana seed extract orally for 1 week, then on day 7 injected with MTX, and continued with guarana for extra 5 days. Blood was taken for biochemical measurement (hormones, antioxidants, cytokines, and oxidative stress biomarkers). Testicular tissues were taken for gene quantification (qRT-PCR), testicular oxidative stress activity (malondialdehyde; MDA, and SOD) and comet assay (sperm DNA damage), and histopathological changes at the end of experimental design. MTX intoxication caused a decrease in testicular SOD, GSH, and catalase and an increase in serum and tissue levels of MDA. Biomarkers of oxidative stress were increased by MTX intoxication, and were ameliorated by guarana administration to MTX-intoxicated mice. Guarana prevented the increase in IL-1ß and IL-6 levels compared to mice intoxicated with MTX alone. MTX upregulated the expression of caspase-3 and downregulated Bcl-2 expression using qRT-PCR analysis. These negative impacts of MTX were protected by guarana pre-administration. MTX decreased reproductive hormones and altered spermogram parameters (sperm concentration and motility, and percentage of live and dead sperms). In addition, the mRNA expression of steroidogenesis-associated genes, such cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 17ß hydroxyl steroid dehydrogenase (17ß-HSD) was downregulated in the MTX-treated group, all were prevented by guarana administration. The sperm DNA damage revealed by a comet assay was increased in MTX group and was reversed to control levels by guarana supplementation. Finally, testis histology of MTX-group showed marked spermatocytes vacuolization and a decrease in spermatogenesis. Guarana administration abrogated histopathological changes reported in the Leydig cells and testicular tissues. In conclusion, guarana has the potential as a supplement medication to antagonize testicular oxidative stress induced by methotrexate.

An In Vitro and In Silico Perspective Study of Seed Priming with Zinc on the Phytotoxicity and Accumulation Pattern of Arsenic in Rice Seedlings.

Arsenic (As) contamination of the rice agro-ecosystem is a major concern for rice farmers of South East Asia as it imposes a serious threat to human and animal life; thus, there is an unrelenting need to explore the ways by which arsenic stress mitigation could be achieved. In the present investigation, we explore the effect of zinc (Zn2+) supplementation using the seed priming technique for the mitigation of As-induced stress responses in developing rice seedlings. In addition to the physiological and biochemical attributes, we also studied the interactive effect of Zn2+ in regulating As-induced changes by targeting antioxidant enzymes using a computational approach. Our findings suggest that Zn2+ and As can effectively modulate redox homeostasis by limiting ROS production and thereby confer protection against oxidative stress. The results also show that As had a significant impact on seedling growth, which was restored by Zn2+ and also minimized the As uptake. A remarkable outcome of the present investigation is that the varietal difference was significant in determining the efficacy of the Zn2+ priming. Further, based on the findings of computational studies, we observed differences in the surface overlap of the antioxidant target enzymes of rice, indicating that the Zn2+ might have foiled the interaction of As with the enzymes. This is undoubtedly a fascinating approach that interprets the mode of action of the antioxidative enzymes under the metal/metalloid-tempted stress condition in rice by pointing at designated targets. The results of the current investigation are rationally significant and may be the pioneering beginning of an exciting and useful method of integrating physiological and biochemical analysis together with a computational modelling approach for evaluating the stress modulating effects of Zn2+ seed priming on As-induced responses in developing rice seedlings.

Phytogenic compounds from avocado (Persea americana L.) extracts; antioxidant activity, amylase inhibitory activity, therapeutic potential of type 2 diabetes.

Diabetes is a worldwide public health disease. Currently, the most effective way to treat diabetes is to mitigate postprandial hyperglycemia by inhibiting carbohydrate hydrolysis enzymes in the digestive system. Plant extracts are rich in bioactive compounds, which can be used in diabetes treatment. This study aims to evaluate the polyphenols content in ethanolic extracts of avocado fruit and leaves (Persea americana Mill.). Additionally, their antioxidant activity using DPPH, while the inhibition ability of α-amylase was examined by reacting different amounts of the extracts with α-amylase compared to acarbose as standard inhibitor. The active compounds were detected in the extracts by LC/MS. The obtained results showed that the leaf extract recorded a significant content of total phenolic compounds compared to the fruit extract (178.95 and 145.7 mg GAE /g dry weight, respectively). The total flavonoid values ​​ranged from 32.5 to 70.08 mg QE/g dry weight of fruit and leaves extracts, respectively. Twenty-six phytogenic compounds were detected in leaf and fruit extract by LC/MS. These compounds belong to fatty acids, sterols, triterpenes, phenolic acids, and flavonoids. The antioxidant activity of the extracts is due to the exist of phytogenic compounds, i.e., polyphenols and flavonoids. The antioxidant activity increased in a concentration dependant manner. Avocado fruit extract (1000 µg/mL) scavenged 95% of DPPH while leaf extract rummaged 91.03% of free radicals compared with Vit C and BHT. Additionally, higher α-amylase inhibitory activity was observed in fruit extract than the leaf extract, where the fruit and leaf extract (1000 µg/ml) inhibited the enzyme by 92.13% and 88.95%, respectively. The obtained results showed that the ethanolic extracts of avocado could have a significant impact on human health due to their high content of polyphenols.

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

Characterization and phytochemical constituents of Periploca hydaspidis Falc crude extract and its anticancer activities.

The current study aims to investigate the anticancer potential of Periploca hydaspidis extracts against HCCLM3 and MDA-MB 231 cell lines with invasive properties and to identify molecular targets underlying its action mechanism. Cytotoxic screening of plant extracts was done via MTT assay against liver and breast cancer cell lines and GC/MS of the best cytotoxic fraction was performed to identify its chemical composition. Flow cytometry detected apoptosis and cell-cycle changes after drug treatment. The specified cells were studied for migration and invasion potential along with performing western blot analysis of proteins involved in apoptosis, cell-cycle, metastasis, and MAPK (Mitogen-activated protein kinase) cell-signaling pathway. The results revealed the crude methanol (PHM) fraction of P. hydaspidis shown dose and time dependent cell-proliferative inhibition response. GC/MS analysis detected 54 compounds of which fatty acids (29.8%), benzenoids (15.7%), and esters (14.3%) constituted the bulk. The inhibitory effect against cancer cells was linked with cell-cycle arrest at G0/G1 phase, induction of apoptosis, reduced migration and invasion capabilities post treatment. PHM induced apoptosis via downregulation of anti-apoptotic (survivin, B-cell lymphoma Extra-large; BCL-XL, X-linked inhibitor of apoptosis protein; XIAP, Myelocytomatosis; C-myc), metastatic (Matrix metallopeptidases 9/2; MMP9/2), and cell-cycle regulatory (cyclin D1 and E) proteins, whereas upregulation of pro-apoptotic proteins (Bcl-2 homologous antagonist/killer; BAK, Bcl-2-Associate X protein; BAX, cleaved caspases; 3,7,8,9, and PARP) and activation of MAPK (Jun amino-terminal kinase; JNK and P38) pathway. P38 was needed for PHM-induced apoptosis, where the inhibition of P38 by pharmacological inhibitor (SB239063) diminished the apoptotic effects. Overall, our results conclude that PHM can inhibit cell-proliferation and induce apoptotic effects by activation of P38 MAPK cell-signaling pathway. This suggests the methanol fraction of P. hydaspidis (PHM) to have anticancer compounds, potentially useful for treating liver and breast cancer. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area.

A strategy for mitigating avian colibacillosis disease using plant growth promoting rhizobacteria and green synthesized zinc oxide nanoparticles.

Avian colibacillosis caused by the zoonotic pathogen Escherichia coli is a common bacterial infection that causes major losses in the poultry sector. Extracts of different medicinal plants and antibiotics have been used against poultry bacterial pathogens. However, overuse of antibiotics and extracts against pathogenic strains leads to the proliferation of multi-drug resistant bacteria. Due to their environmentally friendly nature, nanotechnology and beneficial bacterial strains can be used as effective strategies against poultry infections. Green synthesis of zinc oxide nanoparticles (ZnO-NPs) from Eucalyptus globulus leaves was carried out in this study. Their characterization was done by UV-vis spectroscopy, X-ray diffraction (XRD), and Fourier transmission infrared spectroscopy (FT-IR) which confirmed their synthesis, structure, and size. In vitro, antimicrobial activities of plant leaf extract, ZnO-NPs, and plant growth-promoting rhizobacteria (PGPR) were checked against E. coli using well diffusion as well as disc diffusion method. Results proved that the antimicrobial activity of ZnO-NPs and PGPR strains was more enhanced when compared to eucalyptus leaf extract at 36 h. The maximum relative inhibition shown by ZnO-NPs, PGPR strains and eucalyptus leaf extracts was 88%, 67% and 58%, respectively. The effectiveness of ZnO-NPs was also increased with an increase in particle dose and treatment time. The 90 mg/ml of ZnO-NPs was more effective. PGPR strains from all over the tested strains, Pseudomonas sp. (HY8N) exhibited a strong antagonism against the E. coli strain as compared to other PGPR strains used in this study. However, combined application of PGPR (Pseudomonas sp. (HY8N)) and ZnO-NPs augment antagonistic effects and showed maximum 69% antagonism. The study intends to investigate the binding affinity of ZnO-NPs with the suitable receptor of the bacterial pathogen by in silico methods. The binding site conformations showed that the ligand ZnO binds with conserved binding site of penicillin-binding protein 6 (PBP 6) receptor. According to the interactions, ZnO-NPs form the same interaction pattern with respect to other reported ligands, hence it can play a significant role in the inhibition of PBP 6. This research also found that combining ZnO-NPs with Pseudomonas sp. (HY8N) was a novel and effective technique for treating pathogenic bacteria, including multidrug-resistant bacteria.

Hepatoprotective effect of Thymus vulgaris extract on sodium nitrite-induced changes in oxidative stress, antioxidant and inflammatory marker expression.

The herb thyme (Thymus vulgaris) has multiple therapeutic uses. In this study, we explored how T. vulgaris leaf extract protects liver cells against sodium nitrite-(NaNO2) induced oxidative stress. Mice were divided into four groups; each group received one of the following treatments orally: saline; T. vulgaris extract alone; NaNO2 alone; or T. vulgaris extract + NaNO2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), IL-1ß, IL-6, TNF-α, and total proteins were measured in serum using standard methods. TNF-α, hemooxygenase-1 (HO-1), thioredoxin, SOD, and GSH synthase, all of which are linked to oxidative stress, were measured using quantitative real-time PCR (qRT-PCR). In mice treated with T. vulgaris extract, the effect of NaNO2 on ALT and AST levels and total proteins was reduced, and its effect on antioxidant levels was reversed. Normally, NaNO2 causes hepatocyte congestion and severe hepatic central vein congestion. Tissues in the mice treated with T. vulgaris were restored to normal conditions. Our results demonstrate that NaNO2-induced hepatic injury is significantly reduced by pretreatment with T. vulgaris extract, which protects against hepatic oxidative stress and its associated genes at the biochemical, molecular, and cellular levels.

Ameliorative impacts of Allium cepa Linnaeus aqueous extract against testicular damage induced by dexamethasone.

The present study aimed to explore the impact of onion (Allium cepa Linnaeus) extract on testicular damage induced by dexamethasone. Forty male Wistar rats were divided into four groups (control, dexamethasone, onion extract and dexamethasone group treated with onion extract). Testosterone levels, antioxidant parameters and the expression of caspase-3 and IL-1ß, IL-12, IL-10 genes, as well as histopathological examination and immunohistochemical studies of Bcl2 and caspase-9 expression, were examined. Dexamethasone was found to decrease GSH, total antioxidant activity and testosterone levels, meanwhile treatment with onion extract normalised these levels. MDA was increased in dexamethasone group but appeared normal in the treated group. Dexamethasone was shown to downregulate IL-10 and IL-2 gene expression. Conversely, IL-1ß and caspase-3 gene expression were upregulated by dexamethasone and normalised in the treated group. Histopathological analysis found that dexamethasone caused atrophy to the seminiferous tubules and degeneration to spermatocytes, and immunohistochemical analysis showed overexpression of caspase-9 and inhibited the expression of Bcl-2 in dexamethasone group. These effects were normalised in the onion extract treated group. In conclusion, onion extract have a preventative effect against dexamethasone-induced testicular damage in rats; therefore, its use in complementary therapy is recommended.

Suadian Acacia Gerrardii: Antidiabetic Effect in Rats Suffering from Diabetic Nephropathy and DNA Fingerprinting Using ISSR.

BACKGROUND AND OBJECTIVE: There is a widespread use of medicinal herbs with beneficial uses against different diseased conditions. This study was carried out to identify and study the biological effect of Acacia gerrardii leaf extract on lowering blood sugar in rats suffering from diabetic nephropathy. MATERIALS AND METHODS: It studied the effects of leaf extract at concentrations ranging from 100-500 mg kg-1 b.wt. per day for 4 weeks. Serum glucose levels, total lipids profile and kidney functions were estimated. Plasma levels of sodium and potassium as well as total bilirubin levels were assessed and kidneys from different groups were histopathologically examined. RESULTS: The results showed that leaves were rich in the major compounds of phenolic acids, including salicylic acid and flavonoids with reduction of total lipids, triglycerides and total cholesterol in diabetic rats with renal failure together with reduction in uric acid, creatinine and urea with reduced vacuolar degeneration of tubules and basement membrane thickening. Additionally, the phylogenetic analysis using ISSR primers detected a genetic divergence among different samples. The results showed that the rich antioxidant content of Acacia gerrardii improved lipid, serum antioxidant and kidney function profiles in diabetic rats. CONCLUSION: Acacia gerrardii could be used as a safe source of antioxidants. Moreover, the ISSR assay proved its usefulness in detecting genetic variations among different Acacia gerrardii samples.

Molecular and Histopathological Study on the Ameliorative Impacts of Petroselinum Crispum and Apium Graveolens against Experimental Hyperuricemia.

Hyperuricemia is an abnormal metabolic condition characterized by an increase in uric acid levels in the blood. It is the cause of gout, manifested by inflammatory arthritis, pain and disability. This study examined the possible ameliorative impacts of parsley (PAR) and celery (CEL) as hypouricemic agents at biochemical, molecular and cellular levels. PAR and CEL alone or in combination were orally administered to hyperuricemic (HU) mice and control mice for 10 consecutive days. Serum levels of uric acid and blood urea nitrogen (BUN), xanthine oxidase activity, antioxidants, inflammatory (IL-1ß and TNF-α) and anti-inflammatory cytokines (IL-10) were measured. mRNA expression of urate transporters and uric acid excretion genes in renal tissues were examined using qRT-PCR (quantitative real time PCR). Normal histology and immunoreactivity of transforming growth factor-beta 1 (TGF-ß1) in kidneys was examined. Administration of PAR and CEL significantly reduced serum BUN and uric acids in HU mice, ameliorated changes in malondialdehyde, catalase, and reduced glutathione, glutathione peroxidase (GPX), IL-1ß, TNF-α and IL-10 in hyperuricemic mice. Both effectively normalized the alterations in mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expression, as well as changes in TGF-ß1 immunoreactivity. Interestingly, combined administration of PAR and CEL mitigated all examined measurements synergistically, and improved renal dysfunction in the hyperuricemic mice. The study concluded that PAR and CEL can potentially reduce damaging cellular, molecular and biochemical effects of hyperuricemia both individually and in combination.

Protective Impacts of Moringa oleifera Leaf Extract against Methotrexate-Induced Oxidative Stress and Apoptosis on Mouse Spleen.

OBJECTIVE: The current study was aimed to examine the possible ameliorative impacts of MO leaf extract (MOLE) against MTX-induced alterations on oxidative stress of mouse spleen and explore the possible molecular mechanism that controls such impacts. METHODS: Adult male mice were allocated into 4 groups: control, Moringa oleifera leaf extract (MOLE), MTX, and MOLE plus MTX. Mice received MOLE orally for a week before MTX injection and continued for 12 days. Serum and spleen were sampled for biochemical and quantitative gene expressions. RESULTS: As compared with the MTX-injected group, MOLE effectively reduced the changes in total proteins, spleen MDA, SOD and catalase activities, and changes in serum antioxidants levels. Moreover, there is downregulation of antioxidant genes (SOD and catalase) and antiapoptotic genes (XIAP and Bcl-xl) along with upregulation in Bax and caspase-3 mRNA (apoptotic genes) in the MTX-injected group. MTX induced changes in IL-1ß, IL-6, TNF-α, and IL-10 expression. MOLE restored and ameliorated the changes induced in biochemical, antioxidants, apoptosis, and apoptosis associated genes that were induced by MTX intoxication. CONCLUSION: Current findings indicated that pretreatment with MOLE to MTX-intoxicated mice showed the potential usage of MO for oxidative stress and apoptosis treatment.

The ameliorative impacts of Moringa oleifera leaf extract against oxidative stress and methotrexate-induced hepato-renal dysfunction.

Moringa Oleifera (MO) is a herbal plant native to South Asia known for its anti-oxidative and anti-inflammatory properties. This study explored the protective effects of MO leaf extract (MOLE) against oxidative stress and hepatic and renal injuries caused by methotrexate (MTX) therapy. Mice received a single intraperitoneal injection of 20 mg/kg body weight MTX to induce hepatic and kidney injuries. They then received 300 mg/kg body weight of MOLE orally for seven days, followed by MTX on day 7 then five more days of MOLE (12 days total). Blood, liver and kidney samples were collected from all groups and the following biochemical parameters were tested: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase, superoxide dismutase (SOD), malondialdehyde (MDA) and total proteins. Quantitative real time PCR (qRT-PCR) was used to examine Nrf2, HO-1, BAX, TIMP, XIAP, and NFkB, which are associated with apoptosis, anti-apoptosis and oxidative stress. Capase-9 and Bcl2 genes underwent immunohistochemical analysis. Pretreatment with MOLE reduced the effect of MTX on ALT, AST and total proteins, and reversed its effect on serum and tissue antioxidants. Nrf2/HO-1, apoptotic and anti-apoptotic gene expression was regulated, and Bax and TIMP were reduced; XIAP expression was increased in both the liver and kidney samples, and immunoreactivity of caspase-9 and Bcl2 was restored in the MOLE-administered experimental group. Overall, the study concluded that MOLE can inhibit the effects of hepato-renal injuries caused by MTX by regulating oxidative stress, apoptosis and anti-apoptotic genes at biochemical, molecular and cellular levels.

Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats.

This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both kidney and heart. The probable underlying mechanism of E. peplus compounds to potentiate p53 activity is examined using Molecular Operating Environment (MOE) docking software and validated experimentally by immunohistochemical localization of p53 protein in the kidney and heart tissues. The gas chromatography/mass spectrometry analysis of E. peplus revealed the presence of nine different compounds dominated by di-(2-ethylhexyl) phthalate (DEHP). Significant elevations of troponin, creatine phosphokinase, creatine kinase-myocardium bound, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and uric acid were evident in the EPME treated rats. The EPME treated rats showed strong renal and cardiac p53 expression and moderate cardiac TNF-α expression. Further, our in silico results predicted the higher affinity and good inhibition of DEHP, glyceryl linolenate, and lucenin 2 to the MDM2-p53 interface compared to the standard reference 15 a compound. Conclusively, EPME long-term exposure could adversely affect the cardiac and renal tissues probably due to their inflammatory and apoptotic activity. Moreover, the in silico study hypothesizes that EPME inhibits MDM2-mediated degradation of p53 suggesting possible anticancer potentials which confirmed experimental by strong p53 expression in renal and cardiac tissues.

Hypoglycemic and antioxidant effect of Juniperus procera extract on rats with streptozotocin-induced diabetes.

Juniperus procera, a coniferous tree in the cypress family, is one of the famous medicinal plants traditionally used in the southern area of the Arabian peninsula. This study examined the anti-hyperglycemic action of Juniperus procera extract (JPE) on diabetic rats. Sixty male rats were divided into 6 equal groups: control, control treated with JPE (200 mg/kg), diabetic, diabetic treated with insulin (1 U/kg), diabetic treated with JPE (200 mg/kg), and diabetic treated with both insulin and JPE. Blood and tissue samples were collected for serum chemistry, gene expression, and immunohistochemistry analyses, the results of which revealed hyperglycemia and inflammation following diabetes induction. Administration of JPE alone or with insulin reduced the hyperglycemia reported in diabetic rats by 25 %. The immunohistochemical examination of pancreatic tissues demonstrated a moderate restoration of insulin and NF-κB expression in pancreatic and hepatic tissues. Significant recovery was observed for glutathione-S-transferase (GST), superoxide dismutase (SOD), and glutathione peroxidase (GPx) mRNA expression in the livers of rats treated with JPE. Administration of JPE led to similar amelioration of the mRNA expression of pyruvate kinase (PK) and phosphoenol pyruvate carboxy kinase (PEPCK) in the livers of diabetic rats. In addition, diabetic rats treated with insulin, JPE, or a combination of these agents demonstrated an improvement in the mRNA expression of IRS-1 and IRS-2 in hepatic and pancreatic tissues, reaching levels approaching normal. Our findings led us to conclude that JPE has a powerful anti-inflammatory effect accompanied by a moderate hypoglycemic effect that occurs via different mechanisms.