Pharmacological bioactivity of Ceratonia siliqua pulp extract: in vitro screening and molecular docking analysis, implication of Keap-1/Nrf2/NF-ĸB pathway.

Inflammation is interfaced with various metabolic disorders. Ceratonia siliqua (CS) has a higher pharmaceutical purpose. The research aimed to investigate the biofunction of CS pulp aqueous extract (CS-PAE) with an emphasis on its integrated computational approaches as opposed to different specific receptors contributing to inflammation. The extract was assessed for its chemical and phenolic components via GC-MS, LC-MS, HPLC, and total phenolic and flavonoid content. In vitro, bioactivities and molecular docking were analyzed. Findings indicate that CS-PAE demonstrated higher scavenging activities of nitric oxide, 1,1-diphenyl-2-picrylhydrazyl radical, superoxide anion, hydrogen peroxide, and anti-lipid peroxidation (IC50 values were 5.29, 3.04, 0.63, 7.35 and 9.6 mg/dl, respectively). The extract revealed potent inhibition of RBCs hemolysis, acetylcholine esterase, monoamine oxidase-B, and α-glucosidase enzymes (IC50 was 13.44, 9.31, 2.45, and 1.5 mg/dl, respectively). The extract exhibited a cytotoxic effect against prostate cancer Pc3, liver cancer HepG2, colon cancer Caco2, and lung cancer A549 cell lines. Moreover, CS-PAE owned higher antiviral activity against virus A and some bacteria. When contrasting data from molecular docking, it was reported that both apigenin-7-glucoside and rutin in CS-PAE have a good affinity toward the Keap-1/Nrf2/ NF-ĸB pathway. In conclusion, CS-PAE showed promise in therapeutic activity in metabolic conditions.

Therapeutic Screening of Herbal Remedies for the Management of Diabetes.

The study of diabetes mellitus (DM) patterns illustrates increasingly important facts. Most importantly, they include oxidative stress, inflammation, and cellular death. Up to now, there is a shortage of drug therapies for DM, and the discovery and the development of novel therapeutics for this disease are crucial. Medicinal plants are being used more and more as an alternative and natural cure for the disease. Consequently, the objective of this review was to examine the latest results on the effectiveness and protection of natural plants in the management of DM as adjuvant drugs for diabetes and its complex concomitant diseases.

Characterization of immunological, biochemical and inflammatory response of clinical and subclinical endometritis in ewes in the subtropics.

Pluriparus Ossimi (n = 50) ewes were used to investigate the immune profile of the affected ewes to accurately diagnose clinical and subclinical endometritis and associations with biochemical variables. Ewes were slaughtered and animals were classified into control (no fertility problems), subclinical endometritis (SCE) and clinical endometritis (CE) groups based on pre-slaughter determinations of conception failure. Serum was collected from ewes to estimate concentrations of pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) as well as nitric oxide (NO) concentration. The results from immunological evaluations indicated there were greater (P < 0.001) serum concentrations of IL-6, IL-8, TNF-α and NO in ewes classified with SCE and CE as compared to ewes of the control group. Furthermore, values for concentrations of TNF-α were positively correlated with IL-6 and IL-8 concentrations in ewes of the SCE and CE groups. In ewes classified with CE and SCE there were greater (P < 0.01) concentrations of blood glucose, ALT, AST, urea and creatinine than in ewes of the control group. It is concluded that serum pro-inflammatory cytokines IL-6, IL-8, and TNF-α are diagnostic markers for CE and SCE in ewes and serve as a criterion for different inflammatory complications in ewes classified as having CE or SCE.

The functional nutritional and regulatory activities of calcium supplementation from eggshell for obesity disorders management.

The present study was to investigate the effective role of renewable sources of Ca+2 from eggshell (ES) with different doses to restrict obesity disorders. Rats were classified as follows, G1 : normal diet for 26 weeks; G2 : high-fat diet (HFD) for 26 weeks; G3 , G4 , and G5 were supplemented with HFD for 16 weeks and treated with 7.2 g Ca+2 ES/Kg rat chow, 18 g Ca+2 ES/Kg rat chow, and 2% diet containing fat (DCF), respectively, for the remaining 10 weeks. Results revealed a significant effect of the low dose of Ca+2 supplement in form of ES than high dose and 2% DCF; on basis of anthropometric parameters, lipid, leptin, adiponectin, thyroid hormones, Ca+2 , 25-hydroxyl vitamin-D, and oxidative and inflammatory parameters were regulated. Results were confirmed with the histopathological study. Therefore, it was concluded that Ca+2 supplementation can be used as a beneficial source for obesity management with anticholesterol actions. PRACTICAL APPLICATIONS: Obesity represented public health hazards. The eggshell is one of the waste products that contain a high percentage of Ca+2 . The current data exposed using a low dose of ES as a new source of Ca+2 supplement for treatment of HFD rats leads to significant enhancement of lipid profiles, liver enzymes, kidney functions, leptin, adiponectin, Ca+2 , 25(OH)-D, TSH, fT4, and PTH levels. Also, there was a reduction in weight gain, Bwt, BMI, BG, insulin, and HOMA-IR. Moreover, the oxidant-pro-oxidant system was improved in both hepatic and adipose tissues where NO and TBARS concentrations were diminished, and SOD specific activity was elevated. Additionally, TNF-α and ADAM17 expression were downregulated. Hence, it was concluded that there was good evidence that diets supplemented with ES were associated with the reduction of obesity complications especially regulating fat processing and storage in the body.

Impact of thermal stress exposure on seminal quality, antioxidant defence system, TNF-α and TIMP-3 in Ossimi ram.

Heat stress (HS) occupies huge importance nowadays as it leads to severe economic losses especially in livestock. Preserving sheep against HS is one of the governmental scopes where it represents huge percentage of global ruminant. The present research was conducted to study semen quality, some stress and inflammatory markers in Ossimi rams under both hot and mild climatic conditions. The current study was conducted on selected 46 ram samples divided into two groups during summer and winter. Semen analysis, testosterone (TES), cortisol (COR) and blood glucose (BG) levels, and lipid and protein profiles were done. Concentrations of tumour necrosis factor alpha (TNF-α), tissue inhibitor of metalloproteinase-3 (TIMP-3), nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) and specific activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed. The results in summer compared to winter revealed significant elevation of total defects and number of dead sperms; however, there was reduction in sperm total motility and concentration and external epididymal tail duct diameter. Histological study of epididymal tail lumen exhibited azoospermia. Further, TES, TIMP-3 and GSH levels were decreased and COR, TNF-α, NO and MDA were raised. Specific activities of GPx and SOD were also declined. Additionally, there was a significant increase in concentrations of BG and lipid profiles except high-density lipoprotein. Our data concluded that there were new insights into TNF-α and TIMP-3 as biomarkers can be used in diagnosis of sheep suffering from HS, but further studies are recommended to do in future work about such aspect.

Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome induced in rats.

The liver is the main organ involved in lipid metabolism process and it helps in drug detoxification. Insulin resistance is considered one of risk reasons which lead to several metabolic diseases. Currently, berberine (BER) occupies a huge challenge against multiple diseases with no toxic effect. The present work was aimed to identify, does BER-chloride has a poisonous influence on the liver? and investigating the outcome of BER-chloride on PI3K/Akt-p/SIRT-1/PTEN pathway during insulin resistance syndrome. The insulin resistance model was achieved in experimental female rats via high-fat diet (HFD). Glucose, insulin, lipid profiles, and hepatic oxidative stress parameters were assessed. PI3K, AKt-p, SIRT-1, and PTEN levels in hepatic tissue were determined at genome and protein levels. Further adiponectin concentration was performed in serum, hepatic, and white adipose tissues. Molecular study of fold alteration in insulin, insulin receptor, and retinol binding protein-4 (RBP4) in liver was done. PRACTICAL APPLICATIONS: Obesity syndrome causes multiple obstacles in modern years. The current results revealed elevation the body weight of rats, plasma glucose, homeostatic model assessment, glycated hemoglobin, insulin, and lipid profiles concentrations in a group of rats, which nourished HFD for 8 weeks and this rise, was diminished after 2 weeks from BER-chloride administration. Further, BER-chloride improved transaminases enzymes, pro-oxidant, and antioxidant defense system, PI3K, AKt-p, SIRT-1, and PTEN in the liver, with downregulation of hepatic RBP4. Hence, these data provide a crucial message that BER-chloride enhanced both hepatic function and insulin signaling pathways that might be of therapeutic importance to insulin resistance with no harmful effect on the liver. BER-chloride is predicted to be a drug of choice for obesity complications cure.

Zinc and curcumin lower arylsulfatses and some metabolic parameters in streptozotocin-induced diabetes.

In rats with induced diabetes, Zinc and curcumin treatment showed a significant increase of catalase and a significant decrease of glucose, lipid profile components and arylsulphatases activity compared to the untreated rats. We suggest that dietary zinc and curcumin are promising protective agents for reducing the metabolic defect of diabetes.

Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet.

The black cumin (Nigella sativa) "NS" or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.