An overview on cardioprotective and anti-diabetic effects of thymoquinone

Thymoquinone(TQ), one of the active components of Nigella sativa exhibited to have many biological effects. Several beneficial effects of TQ such as its antidiabetic, antioxidant, anticancer, hypolipidemic, and anti-inflammatory activities have been recognized. The present review focuses on the findings of recent studies on the protective effects of TQ against cardiovascular diseases. In the current review, we additionally concluded that TQ may be therapeutically effective agents for controlling diabetes and hyperlipidemia by decreasing the oxidative stress and inflammatory responses.     

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract

ObjectiveTo explore the antidiabetic properties of Mucuna pruriens(M. pruriens).MethodsDiabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice.ResultsResults showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes.ConclusionsThe study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug.     

Amelioration of alloxan induced diabetes mellitus and oxidative stress in rats by oil of Eruca sativa seeds

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with diabetes mellitus (DM). Oil of Eruca sativa seeds (ESS) is tried for prevention and treatment of DM induced experimentally by alloxan injection. A single dose of alloxan (100 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides and cholesterol, decreased high-density lipoprotein and hepatic glycogen contents and elevated hepatic glucose-6-phosphatase activity. Concurrent with these changes, there was an increase in the concentration of malondialdehyde and 4-hydroxynonenal in the liver. This oxidative stress was related to a decreased glutathione (GSH) content and superoxide dismutase activity in the liver of alloxan-diabetic rats. ESS oil (0.06 ml/kg) on its own increased significantly hepatic GSH. Daily oral administration of ESS oil 2 weeks before or after diabetes induction ameliorated hyperglycemia, improved lipid profile, blunted the increase in malondialdehyde and 4-hydroxynonenal and stimulated the GSH production in the liver of alloxan-treated rats. We suggested that ESS oil could be used as antidiabetic complement in case of DM. This may be related to its antioxidative properties and to the increase in hepatic GSH.     

Regulation of glucose transporter-4 intervention with S. saman leaves extract in streptozotocin-induced diabetic rats

Diabetes mellitus is the leading disorder and affects more than millions of people worldwide. Nowadays, the usage of herbal drugs is said to control adiposity and hyperglycemia. The current research investigated the anti-adiposity and antidiabetic activity of S. saman leaf extract and bioactive compounds. Therefore, the results lower the sugar absorption into the blood and reveal the extract's antidiabetic properties. STZ-induced diabetic rats, Samanea saman methanolic extract show improvement in the parameters like fasting blood glucose levels, body weight, other biochemical parameters supported by the histopathological analysis, and an increase in serum levels in the experimental groups. The antioxidant plays a vital role by increasing SOD and catalase activity levels and decreasing lipid peroxidation levels. The methanolic extract protects the tissue from oxidation stress, which is responsible for the glycemic properties. According to the findings, diabetic-treated rats had overnight blood glucose levels lower and near standard biochemical markers. Histopathology of the liver, pancreas, kidneys, and adipose tissues supported the pharmacological observations.Further, we screened and documented S. saman extract used for in vitro and in vivo methods. In terms of effectiveness, the crude extracts exhibit 0.8-fold GLUT4 down-regulation. Consequently, this result contributes to clinical trials and develops antidiabetic therapy as a substitute for synthetic pharmaceuticals.     

Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an experimental model. METHODS: Male Wistar albino rats were assigned into 4 groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 ml/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis. RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue. CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity.     

Antiproliferative and Apoptosis-Inducing Activities of Thymoquinone in Lymphoblastic Leukemia Cell Line

Acute lymphoblastic leukemia is one of the malignant proliferations of lymphoid cells in the early stages of differentiation and accounts for about 80% of all cases of childhood leukemia. Side effects of available treatment are still main concern. Thymoquinone (TQ), a natural compound isolated from Nigella sativa, induces growth inhibition and apoptosis in several cancer cell lines. The aim of the present study was to investigate the effect of TQ alone and in combination with doxorubicine on the proliferation inhibition and apoptosis induction of TQ in a lymphoblastic leukemia cell line. Jurkat cell line was cultured in standard condition and with concentrations of TQ (0–30 μm) and doxorubicine for 24, 48 and 72 h. Cell viability was measured by MTS assay. Apoptosis induction by TQ was assessed by annexin V-FITC/PI and flow cytometry analysis. TQ and DOX decreased cell viability with a time and dose dependent manner. The IC50 values were 19.461 ± 1.141, 17.342 ± 1.949 and 14.123 ± 1.874 μM in 24, 48 and 72 h, respectively for TQ. IC50 values for DOX were. 075 ± .0124, .028 ± .007 and.007 ± .001 μM in 24, 48 and 72 h, respectively. The level of cell apoptosis in all used concentrations of TQ (4, 8, 12, 16 and 20 μm) was higher than control group (10.2, 14.1, 36.6, 87.5 and 93.3% respectively after 24 h; 10.7, 13.9, 64.6, 92.2 and 93.1 respectively after 48 h; 2.83, 5.83, 41.4, 71.6 and 86.6% respectively after 72 h) and reached to a significant level at 12, 16 and 20 μm concentration for 24 and 48 h and 16 and 20 μm for 72 h incubation. Combination of doxorubicine and TQ lead to a synergistic cytotoxicity as compared to any of them alone. The study indicated that TQ is effective on proliferation inhibition and is a strong apoptotic inducer in Jurkat lymphoblastic cell line and has synergistic effect in combination with DOX. This combination strategy can be an alternative way for more powerful anticancer effects. Therefore, the study of the mechanism of apoptosis induction of TQ can be a step forward to in target therapy which might be considered in the future studies.     

Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila

The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adult Drosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.     

Validation of a trauma questionnaire in veteran women

The Trauma Questionnaire (TQ) assesses a woman's history of childhood and adult sexual trauma, sexual harassment, and domestic violence. The TQ is used widely at Veterans Affairs Medical Centers, but its validity has not been thoroughly examined. In a prospective study of 127 women, we found the TQ to have good to excellent agreement with a semistructured clinician interview and good sensitivity and specificity. The TQ can be used as a valid alternative to the clinician interview in the initial elicitation of trauma history among women veterans in the primary care setting. KEY WORDS: trauma; questionnaire; women; veterans.     

Utility of opium seed extract tests in preventing hypersensitivity reactions during surgery

BackgroundAnaphylaxis during anaesthesia is fatal in 3–9% of patients and analgesics, including opioids, and is the second most common medicament-related cause, although the prevalence is underestimated. We recently found that patients may generate IgE antibodies to opium seeds.ObjectivesTo determine the diagnostic accuracy of specific antibodies to morphine, codeine, rocuronium and oil body and aqueous fractions of Papaver somniferum seeds in the diagnosis and prevention of allergy to opioids.MethodsPatients with hypersensitivity reactions during surgery, and severe clinical allergy (pollen, tobacco), and illicit heroin users were selected. The sensitivity, specificity and predictive values of in vivo and in vitro diagnostic techniques including oil body and aqueous fractions of P. somniferum seeds were measured.ResultsWe studied 203 patients, with mean age 35.1 ± 17.1 and 200 healthy controls. Patients sensitised to heroin or with hypersensitivity reactions during surgery responded to P. somniferum seed tests. Of patients not known to be sensitised to opioids, the highest positivity was in patients sensitised to tobacco (p < 0.001). Opium seed skin tests and IgE, especially the oil body fraction, were more sensitive (64.2%) and specific (98.4%) than morphine, codeine and rocuronium tests for opioid sensitivity. Pollen allergy was not a risk factor for sensitisation to morphine.ConclusionsSensitivity to opioids and intraoperative anaphylaxis can be diagnosed by routine tests. IgE and skin tests for the oil body fraction of P. somniferum had the highest sensitivity for sensitisation to opioids.     

Pharmacognostic and phytochemical evaluation of Dolichos biflorus Linn.

ObjectiveTo study in detail the micromorphology and physicochemical analysis of the seeds of Dolichos biflorus Linn. (Family: Papileonaceae).MethodsMacroscopy, microscopy, physicochemical analysis, preliminary phytochemical screening and other WHO recommended parameters for standardizations were performed.ResultsThe seeds are roughly trapezoidal and flattish, with quite thin cotyledons. The hylum is small and linear and located in a small depression on the seed's lateral margin. The length of archeological specimens are usually 3.0–4.0 mm, width 2.0–2.6 mm and thickness 1.4–2.0 mm. Microscopic evaluation revealed the epidermis is single layered brown in colour, thin walled and shining cells because of mucilage in this layer. Endosperm forms bulk of the seed with thick walled polygonal parenchymatous cells. Outer portion of the seed contains alueron grains which are protein in nature. In the mid of the seeds, embryo can be seen which provides nutrition. Preliminary phytochemical screening showed the presence of steroids, tannins, proteins, aminoacids, flavonoids, terpenoids, mucilage, volatileoil, saponin and carbohydrates and absence of alkaloids, fixed oil.ConclusionsThe microscopic using histological identification, microscopic constants and other physico chemical examinations of the seeds of Dolichos biflorus Linn. can be used as a rapid, inexpensive botanical identification technique and is useful in standardization, hence it would be of immense value in authentication of seed.     

L'allergie au tournesol et à son huile : rôles du contact,de l'ingestion et de l'inhalation

We report the case of a 5-years old girl with food allergy to sunflower oil. Sensitivity to sunflower oil and seeds was demonstrated by skin tests whereas assays of serum for sunflower-specific IgE were negative. An oral challenge test with 54 ml of sunflower oil was positive. The patient also reacted to cutaneous contact and inhalation of sunflower seeds. Depending on the route of contact –– skin contact, ingestion or inhalation –– sunflower oil and seeds can trigger symptoms such as urticaria, erythema, vomiting, dyspnea or fatigue.     

Evaluation of antihyperglycemic and antioxidant properties of Streblus asper Lour against streptozotocin–induced diabetes in rats

ObjectiveTo evaluate antidiabetic and antioxidant role of methanol extract of Streblus asper (S. asper) root bark in Wistar rats.MethodsDiabetes was induced in rats by single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight). Three days after STZ induction, the diabetic rats were treated with S. asper orally at dose of 200 and 400 mg/kg body weight daily for 15 days. Glibenclamide (0.25 mg/kg, orally) was used as reference drug. The fasting blood glucose levels were measured on every fifth day during the 15-day treatment. Serum biochemical parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, total cholesterol total protein and serum triglycerides were estimated. Antioxidant properties were assessed by estimating liver and kidney thiobarbituric acid reactive substances, reduced glutathione and catalase.ResultsS. asper in STZ-induced diabetic rats, at doses of 200 and 400 mg/kg bw produced reduction in blood glucose levels when compared with the STZ control group. Serum biochemical parameters antioxidant levels were significantly restored toward normal levels in S. asper treated rats as compared with STZ control.ConclusionsThe present study infers that the methanol extract of S. asper root bark demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats. The potential antidiabetic action is plausibly due to its underlying antioxidant role.     

Usefulness of diastolic time measured on electrocardiogram to improve sensitivity and specificity of exercise tolerance tests

The current exercise tolerance test (ETT) criteria predominantly assess changes in ST-segment deviation (i.e., a systolic component of the cardiac cycle). Because diastolic dysfunction precedes that of systolic dysfunction during myocardial ischemia and most coronary flow is diastolic, the addition of electrocardiographic markers of diastolic time might improve the ETT sensitivity and specificity for detecting significant coronary artery disease. Among consecutive patients who had an ETT and subsequently underwent coronary angiography, we evaluated the diastolic time by assessing the TP and TQ segments and TP/RR and TQ/RR ratios in each ETT stage. Coronary artery disease was defined angiographically as significant (≥70% lumen occlusion), intermediate (>50% but <70% lumen occlusion), or nonsignificant (≤50% lumen occlusion). Of the 48 study patients, hypertension and hyperlipidemia appeared highly prevalent. TP, TQ, TP/RR, and TQ/RR correlated significantly with RR and changed with each ETT stage. Although TP and TQ were not significantly associated with significant coronary artery disease, TP/RR and TQ/RR proved to be, particularly beyond stage 2. When TQ/RR of ≤0.39 and TP/RR of ≤0.13 were used, their individual sensitivities and specificities were reasonably comparable to that of traditional ETT criteria (79% sensitivity and 44% specificity at our institution). Adding TQ/RR of ≤0.39 and/or TP/RR of ≤0.13 to existing ETT criteria improved its sensitivity to 100% and specificity to 86%. In conclusion, the addition of diastolic time indexes of TP/RR and TQ/RR significantly improved the overall ETT diagnostic value above the guideline-oriented, perhaps "traditional," criteria for the diagnosis of myocardial ischemia. Such parameters should be widely investigated further for clinical accuracy and compatibility.     

Antidiabetic effects of sage (Salvia officinalis L.) leaves in normal and streptozotocin-induced diabetic rats

BackgroundSage (Salvia officinalis L.) has a wide range of biological activities, such as anti-oxidative properties, anti-bacterial, hypoglycemic, anti-inflammatory, fungistatic, virustatic, astringent, eupeptic and anti-hydrotic effects. This study was designed to examine the antidiabetic effect of sage ethanolic extract in normal and streptozotocin-induced diabetic rats.MethodsOral administration of sage extract (0.1, 0.2, and 0.4 g/kg body weight) and glibenclamide (600 μg/kg) for 14 days on the level of serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in normal and streptozotocin-induced diabetic rats were evaluated.ResultsOral administration of 0.2 and 0.4 g/kg body wt. of the sage extract for 14 days exhibited a significant reduction in serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, AST, ALT and increased plasma insulin in streptozotocin-induced diabetic rats but not in normal rats. Glibenclamide was used as reference and showed similar antidiabetic effect.ConclusionsIt is concluded that the traditional use of S. officinalis as an antidiabetic agent is justified and that extracts from this plant show a dose-dependent activity which is comparable to the standard antidiabetic drug glibenclamide.     

Local maternal control of seed size by KLUH/CYP78A5-dependent growth signaling

Seed development in plants involves the coordinated growth of the embryo, endosperm, and maternal tissue. Several genes have been identified that influence seed size by acting maternally, such as AUXIN RESPONSE FACTOR2, APETALA2, and DA1. However, given the lack of gain-of-function effects of these genes on seed size, it is unclear whether their activity levels are limiting in WT plants and whether they could thus be used to regulate seed size in development or evolution. Also, whether the altered seed sizes reflect local gene activity or global physiological changes is unknown. Here, we demonstrate that the cytochrome P450 KLUH (KLU) regulates seed size. KLU acts locally in developing flowers to promote seed growth, and its activity level is limiting for seed growth in WT. KLU is expressed in the inner integument of developing ovules, where it non-cell autonomously stimulates cell proliferation, thus determining the growth potential of the seed coat and seed. A KLU-induced increase in seed size leads to larger seedlings and higher relative oil content of the seeds. Genetic analyses indicate that KLU acts independently of other tested maternal factors that influence integument cell proliferation. Thus, the level of KLU-dependent growth factor signaling determines size in ovules and seeds, suggesting this pathway as a target for crop improvement.     

QT restitution properties of middle-aged women with different exercise capacities

Background

Framingham Study data indicate an incremental risk of cardiovascular death in relation to low exercise capacity in women. The reason for death is still not clear.

Methods

QT restitution properties in 80 middle-aged women were investigated to confirm whether the cardiac restitution property was affected by the exercise capacity. Exercise tests were performed according to the Bruce protocol. Seventy cases were divided into the low-exercise capacity group (LEC group) and high-exercise capacity group (HEC group) by median exercise capacities. Sequential QT intervals and their preceding TQ intervals were measured, and the QT restitution curve (QTRC) was constructed. Two exponential equations were used to match the data and calculate the maximum slope (Smax) of QTRC, respectively.

Results

With elevation in the exercise level, the women in the LEC group had a higher change rate of QT intervals (41 ± 10 vs 29 ± 3 ms/Met, P = .001) and TQ intervals (46 ± 12 vs 41 ± 7 ms/Met, P = .046); and the ratio of QT interval alterations to TQ interval alterations increased (0.41 ± 0.09 vs 0.36 ± 0.07, P = .003). The Smax of the QTRC in the LEC group was higher than that in the HEC group (1.43 ± 0.44 vs 1.13 ± 0.34, P = .002). There was an inverse relationship between Smax and exercise capacity (r = −0.43, P = .001).

Conclusion

Middle-aged women with low exercise capacity have steeper QTRCs than those with high exercise capacity, denoting a more unstable alternation of QT interval with elevation in exercise level.