title: Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension Effects of Dapagliflozin, an SGLT2 Inhibitor, on HbA1c, Body Weight, and Hypoglycemia Risk in Patients With Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content Effect of Nigella sativa supplementation over a one-year period on lipid levels, blood pressure and heart rate in type-2 diabetic patients receiving oral hypoglycemic agents: nonrandomized clinical trial Partial regeneration/proliferation of the beta-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats. Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Nutritional intervention in patients with type 2 diabetes who are hyperglycaemic despite optimised drug treatment—Lifestyle Over and Above Drugs in Diabetes (LOADD) study: randomised controlled trial
abstract: Hypertension ( HT ) is a lifestyle‐related disease and dietary modifications are effective for its management and prevention . We conducted a r and omized , double‐blind , placebo‐controlled trial to evaluate the efficacy of treatment with an oral Nigella sativa ( NS ) seed extract supplement in patients with mild HT . Subjects were r and omized into three groups : a placebo and two test groups that received 100 and 200 mg of NS extract twice a day . After 8 weeks , systolic blood pressure ( SBP ) values in both case groups were found to be significantly reduced when compared with the baseline values for each group . In addition , the decrease in SBP in the two case groups was statistically significant relative to the placebo group ( P < 0.05–0.01 ) . Meanwhile , diastolic blood pressure ( DBP ) values in the case groups were found to be significantly reduced from the baseline and a significant reduction was also observed in these groups ( P < 0.01 ) when compared with the placebo group . In addition , extract administration reduced both SBP and DBP in a dose‐dependent manner . Meanwhile , NS extract caused a significant decline in the level of total and low‐density‐lipoprotein (LDL)‐cholesterol relative to baseline data . No complications caused by NS were observed . The results suggest that the daily use of NS seed extract for 2 months may have a blood pressure‐lowering effect in patients with mild HT OBJECTIVE To examine the safety and efficacy of dapagliflozin , a sodium-glucose cotransporter-2 inhibitor , added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone . RESEARCH DESIGN AND METHODS Treatment-naive patients or those receiving metformin , sulfonylurea , or thiazolidinedione  entered a 10-week pioglitazone dose-optimization period with only pioglitazone . They were then r and omized , along with patients previously receiving pioglitazone ≥30 mg , to 48 weeks of double-blind dapagliflozin 5 ( n = 141 ) or 10 mg ( n = 140 ) or placebo  ( n = 139 ) every day plus open-label pioglitazone . The primary objective compared HbA1c change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24 . Primary analysis was based on ANCOVA model using last observation carried forward ; all remaining analyses used repeated- measures analysis . RESULTS At week 24 , the mean reduction from baseline in HbA1c was −0.42 % for placebo versus −0.82 and −0.97 % for dapagliflozin 5 and 10 mg groups , respectively ( P = 0.0007 and P < 0.0001 versus placebo ) . Patients receiving pioglitazone alone  had greater weight gain ( 3 kg ) than those receiving dapagliflozin plus pioglitazone ( 0.7–1.4 kg ) at week 48 . Through 48 weeks : hypoglycemia was rare ; more events suggestive of genital infection were reported with dapagliflozin ( 8.6–9.2 % ) than placebo ( 2.9 % ) ; events suggestive of urinary tract infection showed no clear drug effect ( 5.0–8.5 % for dapagliflozin and 7.9 % for placebo ) ; dapagliflozin plus pioglitazone groups had less edema ( 2.1–4.3 % ) compared with placebo plus pioglitazone ( 6.5 % ) ; and congestive heart failure and fractures were rare . CONCLUSIONS In patients with type 2 diabetes inadequately controlled on pioglitazone  , the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk The antidiabetic effect of N. sativa seed ethanol extract ( NSE ) was assessed in Meriones shawi after development of diabetes . Meriones shawi were divided r and omly into four groups : normal control , diabetic control , diabetic treated with NSE ( 2 g eq plant/kg ) or with metformin ( 300 mg/kg ) positive control , both administered by daily intragastric gavage for 4 weeks . Glycaemia and body weight were evaluated weekly . At study 's end , an Oral Glucose Tolerance Test ( OGTT ) was performed to estimate insulin sensitivity . Upon sacrifice , plasma lipid profile , insulin , leptin , and adiponectin levels were assessed . ACC phosphorylation and Glut4 protein content were determined in liver and skeletal muscle . NSE animals showed a progressive normalization of glycaemia , albeit slower than that of metformin controls . Moreover , NSE increased insulinemia and HDL-cholesterol , compared to diabetic controls . Leptin and adiponectin were unchanged . NSE treatment decreased OGTT and tended to decrease liver and muscle triglyceride content .  NSE stimulated muscle and liver ACC phosphorylation and increased muscle Glut4 . These results confirm NSE 's previously reported hypoglycaemic and hypolipidemic activity . More significantly , our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation , a major component of the insulin-independent AMPK signaling pathway , and by enhancing muscle Glut4 expression BACKGROUND Diabetic patients with hypertension and dyslipidemia are at a high risk of cardiovascular complications . OBJECTIVES To determine the effect of Nigella sativa supplementation on the lipid profile , mean arterial pressure , and heart rate in persons with type 2 diabetes on oral hypoglycemic agents ( OHA ) .  DESIGN Single-blind , nonr and omized . SETTING Diabetes clinic of a university hospital in Saudi Arabia . PATIENTS AND METHODS Type-2 diabetic patients were recruited by purposive sampling and assigned to treatment or control at the discretion of the investigator with the patient blinded to treatment . Before the intervention and every 3 months thereafter until the end of the treatment period , the following parameters were measured : triglycerides ( TG ) , total cholesterol ( TC ) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , heart rate ( HR ) , and body mass index ( BMI ) . Results at the baseline and each subsequent visit were compared between the two groups . MAIN OUTCOME MEASURE(S ) Lipid and cardiovascular parameters , and BMI . RESULTS Fifty-seven patients were assigned to receive N sativa 2 g daily for one year and 57 were assigned to receive an identical regimen of placebo , along with OHA . A significant decrease in HDL-C and increase in the TC/HDL-C and LDL-C/HDL-C ratios were seen in the control group . The N sativa group had a significant decline in TC , LDL-C , TC/HDL-C and LDL-C/HDL-C ratios , compared with the respective baseline data and the control group . HDL-C was significantly elevated in the N sativa group . The control group showed a significant elevation in MAP . The N sativa group had a significant reduction in SBP , DBP , MAP and HR and a significant decrease in DBP , MAP and HR as compared with the control group . CONCLUSION N sativa supplementation improves total cholesterol , mean arterial pressure and heart rate in type 2 diabetes patients on oral hypoglycemic agents .  LIMITATIONS There were 9 subjects in each group lost to follow up ; thus the sample size could not be maintained as per the sample size calculation . The study was nonr and omized and thus there was a possibility of allocation bias . ( Clinical trial registration number : CTRI/2013/06/003781 , Clinical Trial Registry of India ) This experiment was carried out to investigate the effect of N. sativa L. on histopathology of pancreatic beta-cells , and blood insulin and glucose concentrations in streptozotocin-induced diabetic rats . Fifty male Wistar rats ( 200 - 250 g ) were divided into two experimental groups ( diabetics with no treatment and diabetics with N. sativa L. treatment ) , each containing twenty-five rats . Diabetes was induced in both groups by a single intraperitoneal injection of streptozotocin ( STZ ) ( 50 mg/kg ) . The experimental animals in both groups became diabetic within 24 hours after the administration of STZ . The rats in N. sativa L.-treated group were given the daily intraperitoneal injection of 0.20 ml/kg of N. sativa L. volatile oil for 30 days starting the day after STZ injection . Control rats received only the same amount of normal saline solution . The rats in both groups received the last injection 24 hours before the sacrification and 5 r and omly-selected rats in each group were sacrificed before , and the 1 , 10 , 20 and 30 days after the STZ injection to collect blood and pancreatic tissue sample s. The N. sativa L. treatment caused a decrease in the elevated serum glucose , an increase in the lowered serum insulin concentrations and partial regeneration/ proliferation of pancreatic beta-cells in STZ-induced diabetic rats with the elapse of the experiment . It is concluded that the hypoglycaemic action of N. sativa L. could be partly due to amelioration in the beta-cells of pancreatic islets causing an increase in insulin secretion . More studies are needed to demonstrate the exact mechanism of action of N. sativa L. on ameliorated blood glucose concentration in STZ-induced diabetes The constituents of Nigella sativa modulate the immune system . The aim of the present work was to study the effectiveness of Nigella sativa oil in RA patients . Data from 40 female RA patients diagnosed according to the 2010 ACR/EULAR were analysed and discussed . The patients took two placebo ( starch filled ) capsules daily for 1 month . This was followed by a month of Nigella sativa oil capsules 500 mg twice/day . The disease activity score ( DAS-28 ) significantly decreased after receiving the Nigella sativa capsules ( 4.55 ± 0.82 ) compared with before and after placebo ( 4.98 ± 0.79 and 4.99 ± 0.72 , respectively ) ( p = 0.017 ) . Similarly , the number of swollen joints and the duration of morning stiffness improved . A marked improvement in the disease activity was shown by both the ACR20 and EULAR response criteria in 42.5 % and 30 % of the patients , respectively , after intake of Nigella . Supplementation with Nigella sativa during DMARD therapy in RA may be considered an affordable potential adjuvant biological therapy UNLABELLED Diabetes mellitus is a common chronic disease affecting millions of people world wide . St and ard treatment is failing to achieve required correction of blood glucose in many patients . Therefore , there is a need for investigating potential hypoglycemic drugs or herbs to improve glycemic control in diabetic patients .  Nigella sativa seeds were used as an adjuvant therapy in patients with diabetes mellitus type 2 added to their anti-diabetic medications . A total of 94 patient were recruited and divided r and omly into three dose groups . Capsules containing Nigella sativa were administered orally in a dose of 1 , 2 and 3 gm/day for three months . The effect of Nigella sativa on the glycemic control was assessed through measurement of fasting blood glucose ( FBG ) , blood glucose level 2 hours postpr and ially ( 2 hPG ) , and glycosylated hemoglobin ( HbA1c ) . Serum C-peptide and changes in body weight were also measured . Insulin resistance and beta-cell function were calculated usin the homeostatic model assessment ( HOMA2 ) . Nigella sativa at a dose of 2 gm/day caused significant reductions in FBG , 2hPG , and HbA1 without significant change in body weight . Fasting blood glucose was reduced by an average of 45 , 62 and 56 mg/dl at 4 , 8 and 12 weeks respectively . HbAlC was reduced by 1.52 % at the end of the 12 weeks of treatment ( P<0.0001 ) . Insulin resistance calculated by HOMA2 was reduced significantly ( P<0.01 ) , while B-cell function was increased ( P<0.02 ) at 12 weeks of treatment . The use of Nigella sativa in a dose of 1 gm/day also showed trends in improvement in all the measured parameters but it was not statistically significant from the baseline . However , no further increment in the beneficial response was observed with the 3 gm/day dose . The three doses of Nigella sativa used in the study did not adversely affect either renal functions or hepatic functions of the diabetic patients throughout the study period . IN CONCLUSION the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients Objective To determine the extent to which intensive dietary intervention can influence glycaemic control and risk factors for cardiovascular disease in patients with type 2 diabetes who are hyperglycaemic despite optimised drug treatment . Design R and omised controlled trial . Setting Dunedin , New Zeal and . Participants 93 participants aged less than 70 years with type 2 diabetes and a glycated haemoglobin ( HbA1c ) of more than 7 % despite optimised drug treatments plus at least two of overweight or obesity , hypertension , and dyslipidaemia . Intervention Intensive individualised dietary advice ( according to the nutritional recommendations of the European Association for the Study of Diabetes ) for six months ; both the intervention and control participants continued with their usual medical surveillance . Main outcome measures HbA1c was the primary outcome . Secondary outcomes included measures of adiposity , blood pressure , and lipid profile . Results After adjustment for age , sex , and baseline measurements , the difference in HbA1c between the intervention and control groups at six months ( −0.4 % , 95 % confidence interval −0.7 % to −0.1 % ) was highly statistically significant ( P=0.007 ) , as were the decreases in weight ( −1.3 kg , −2.4 to −0.1 kg ; P=0.032 ) , body mass index ( −0.5 , −0.9 to −0.1 ; P=0.026 ) , and waist circumference ( −1.6 cm , −2.7 to −0.5 cm ; P=0.005 ) . A decrease in saturated fat ( −1.9 % total energy , −3.3 % to −0.6 % ; P=0.006 ) and an increase in protein ( 1.6 % total energy , 0.04 % to 3.1 % ; P=0.045 ) in the intervention group were the most striking differences in nutritional intake between the two groups . Conclusions Intensive dietary advice has the potential to appreciably improve glycaemic control and anthropometric measures in patients with type 2 diabetes and unsatisfactory HbA1c despite optimised hypoglycaemic drug treatment . Trial registration Clinical trials NCT00124553
target: Although , the meta- analysis conducted included a few number of studies , but has shown promising results on the effectiveness of N. sativa on glucose homeostasis and serum lipids .
background: BACKGROUND & OBJECTIVE ( S ) Global prevalence of type 2 diabetes ( T2D ) is very high and is currently growing alarmingly .
  With respect to recent research ers ' attention to the potential role of herbal medicine in disease prevention and management , the present meta- analysis review investigates the effectiveness of Nigella sativa ( N. sativa ) , a popular herb , in T2D .