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Effects of black cumin (Nigella sativa) oil administration on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and effective renal blood flow (ERBF). Notes: All data are expressed as mean ± standard deviation. *Indicates significant difference between groups, P , 0.01. Abbreviations: COn, control rats; COn-BC, control rats administered with black cumin oil; sTZ, diabetic rats not administered with black cumin oil; sTZ-BC, diabetic rats administered with black cumin oil.
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Background
Black cumin (Nigella sativa) is an ancient herbal medicine recommended by the World Health Organization. The antioxidant and antihyperglycemic effects of black cumin are well established. Amelioration of renal dysfunction in nephrotoxic rats with black cumin treatment has also been noted. However, the effect of black cumin treatment on r...
Citations
... On the other side, N. sativa decreased the fractional excretion of Mg (++) and water (P < 0.05), thereby recovering the renal tubular dysfunction of the kidney. Overall, N. sativa can be assumed as a potent agent in improving renal hemodynamics and dysfunction (Yusuksawad & Chaiyabutr, 2012). ...
Various studies have been conducted on the effect of medicinal plants in the treatment of different diseases, including diabetes. Nigella Sativa (N. sativa) is a plant with edible and medicinal properties that are of interest to scientists in traditional and complementary medicine, and much research has been conducted on this plant. Comprehensive reports are used to investigate the effect of N. sativa in vitro, animal models, and clinical trials in the treatment of diabetic diseases. An online database search was conducted to investigate the potential anti-diabetic effect of N. sativa. The results of various studies indicate that this plant can act as hypoglycemic, and due to antioxidant properties, it can have positive results in reducing blood sugar and glycosylated hemoglobin levels and controlling insulin secretion and glucose homeostasis. The effect of N. sativa in animal models has shown that N. sativa oil can eliminate oxygen-free radical species similar to hydroxyl free radicals and superoxide radical anions. Therefore, in this review study, we intend to address all the therapeutic aspects and effects of the black seed plant in the cellular and animal environment and clinical trial studies for the optimal use of this medicinal plant. In conclusion, the antidiabetic activities of N. sativa are indeed well established. However, in some cases, the molecular modulation underlying these activities remains unknown. N. sativa has been demonstrated to improve blood glucose and insulin levels, mitigate diabetes complications, and stimulate glucose absorption. Its antioxidant function, flavonoid and triterpenoid components, and potency to modulate insulin secretion in pancreatic cells introduced it as a safe medicinal herb for dietary adjuvant with antidiabetic medications. However, it has been declared to a decline in blood lipid profiles, and risk factors for cardiovascular diseases in Type 2 Diabetes patients. Further research must concentrate on patients unresponsive to available anti-diabetic drugs and hyperlipidemia T2D. Thus, further studies into its medicinal effects are recommended.
... [38] In addition, renal hemodynamics improving effect of black cumin was reported by Yusuksawad and Chaiyabutr who revealed an increased GFR, effective RPF, and effective RBF, while decreased RVR in streptozotocin-induced diabetic rats. [49] This might be explained by Cherkaoui-Tangi et al., who reported a vasorelaxant activity of essential oil of N. sativa seeds on isolated rat aorta. [50] This study has a few limitations, such as sample size: the number of rats used in the study might be limited. ...
Objective
Hypoxia is one of the principal causes of renal diseases. This study aimed to evaluate the effects of Nigella sativa on dinitrophenol (DNP)-induced hypoxia renal damage in rats.
Methods
Forty adult male rats were incorporated in this study. The rats were divided into four groups: control group, N. sativa group, DNP hypoxic group, and DNP + N. sativa group receiving N. sativa (400 mg/kg body weight). Serum and renal tissue erythropoietin (EPO) hormone and hypoxia-inducible factor-2α (HIF-2α) levels were measured. Renal oxidative stress biomarkers, inflammatory biomarkers, renal hemodynamics, and histopathological examination were evaluated.
Results
Administration of N. sativa highly significantly normalized serum EPO level, HIF-2α (P < 0.001 for each) in DNP + N. sativa treated rats as compared to DNP hypoxic rats. Furthermore, it highly significantly improved renal oxidative stress evident by decreased renal tissues malondialdehyde and increased superoxide dismutase, total thiol, and catalase activity (P < 0.001 for each). Furthermore, a highly significant decline of renal intercellular adhesion molecule-1, myeloperoxidase, and interleukin-6 was observed in DNP + N. sativa rats (P < 0.001 for each). Improvements in renal hemodynamics and kidney functions were also found after N. sativa administration (with P < 0.001 for all parameters). In addition, N. sativa treatment reduced renal histopathological changes of the DNP + N. sativa group. Our results were statistically analyzed using the Prism software package (GraphPad version 8.0).
Conclusion
N. sativa has an alleviating effect on DNP-induced hypoxia renal damage and can restore kidney functions in rats’ animal models. These effects were through antioxidant, anti-inflammatory, and hemodynamic mechanisms.
... Type-2 diabetic men and women 94, 3 group 1, 2 and 3 g/day Powdered N. sativa 12 weeks 1 g/day NS seeds showed significant increase in HDL-C; 2 g/day NS displayed a significant decline in TC, TG, and LDL-C, and a significant elevation in HDL-C/LDL-C; only dose of 2 g/day for 12 weeks may improve the dyslipidemia associated with T2DM. Yusuksawad 47 Saudi Arabia 2012 ...
... Researchers have shown a reduction in blood creatinine, urea, and 24 h total urinary protein levels, 29,31,33,87 improved renal tubular dysfunction and restored changes in renal hemodynamics such as increase in glomerular filtration rate, 24 h total urinary volume and hemoglobin levels were measured. 29,31,47 In a study, STZ-induced diabetic rats were supplemented with N. sativa oil and TQ. They exhibited suppression of diabetes-induced downregulation of mRNA expression of the podocin, a protein that plays a role in regulating glomerular permeability, as well as mRNA over expressions of collagen IV, transforming growth factor-β1 and vascular endothelial growth factor-A in the diabetic kidney. ...
Objective
The purpose of this up-to-date comprehensive systematic review was to evaluate and summarize all research studies in the field in order to clarify the magnitude of Nigella sativa (N. sativa) effects on the management of Diabetes mellitus (DM) and its complications.
Methods
A systematic review was conducted in a Cochrane style and in accordance PRISMA checklist using the published studies in PubMed/MEDLINE, SCOPUS, and EMBASE databases that were searched up to January 2019. Abstracts that met PICO criteria for qualitative studies underwent dual review for data extraction to evaluate study quality and details.
Results
Dietary supplementation with N. sativa preparations can improve various secondary complications of diabetic patients. N. sativa preparations possess antidiabetic, hypoglycemic, anti-hyperlipidemic, antihypertensive, and anti-obesity effects. Beneficial effects of N. sativa preparations include the restoration of the antioxidant defense systems, the increase in the activity of antioxidant enzymes, the decrease of inflammatory biomarkers, the suppression of the production pro-inflammatory mediators, improvement of endothelial dysfunction, and hepatic, kidney, heart and immune system functions. They have key roles in managing diabetes-induced inflammation and oxidative stress in diabetic patients.
Conclusion
N. sativa preparations have key roles in herbal medicine as an adjuvant in the treatment and management of patients with DM and its complications. Moreover, the beneficial effects of N. sativa preparations were differently based on dosage forms, active ingredients, and duration of intervention. The best dosage to improve glycemic indices and lipid and lipoprotein profiles is 2 grams daily powdered N. sativa for at least 12 weeks.
... 22 It was observed that administration of N. sativa oil at a dose of 1000 mg/kg body weight/day for eight weeks caused the restoration of renal hemodynamic and functions in streptozotocin-induced diabetic rats in the form of increased GFR and effective renal blood flow. 23 There was a steady rise in serum sodium level; it was within normal physiological range in both the groups, and the results in both groups were statistically significant (P <0.001) at the end of 12 weeks, but Group II showed more marked improvement. Serum potassium level in both the groups reduced steadily, but this change was statistically significant in Group I (P <0.001) as well as in Group II (P <0.001) after 12 weeks of treatment. ...
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysio- logic processes associated with abnormal kidney function. When it reaches end-stage renal disease (ESRD), the only option is dialysis and renal transplantation. This is unaffordable by most patients. Hence, newer treatment modalities are being looked for, which can slow down the progression of CKD and delay the development of ESRD. This study aimed to evaluate the efficacy and safety of Nigella sativa oil as an add-on therapy in addition to alpha-keto analogue of essential amino acids in patients with CKD Stages 3 and 4. The study was conducted at a tertiary care center in North India on patients with CKD Stages 3 and 4. It was a prospective, comparative, and open-labeled study. One hundred and fifty patients were enrolled and were randomly divided into two interventional groups. Fourteen patients were lost to follow-up. Group I (control) which had 66 patients received conservative management of CKD consisting of alpha-keto analogue (600 mg tablet three times a day), whereas Group II (test) which had 70 patients received conservative management along with alpha-keto analogue and N. sativa oil (2.5 mL, per orally, once daily) for 12 weeks. Hemogram, renal function, and serum electrolyte tests were done, and adverse events were recorded at baseline and at4, 8, and 12 weeks of treatment. After 12 weeks of treatment, there was a marked improvement in clinical features and biochemical parameters in both the control and test groups. There were a significant reduction in blood urea, serum creatinine, and 24-h total urine protein and a significant improvement in 24-h total urine volume and glomerular filtration rate. N. sativa oil supplementation along with alpha-keto analogue is more more efficacious and safe in delaying the progression of disease patients with CKD Stages 3 and 4.
... Previous studies also demonstrated that ketoanalogs supplementation exhibited enhancement in GFR in CKD patients (Stages III and IV) [25]. It was also witnessed that administration of N. sativa oil at a dose of 1000 mg/kg body weight/day for 8 weeks caused restoration of renal hemodynamic and functions in streptozotocininduced diabetic rats in the form of increased GFR and effective renal blood flow [26]. The add-on effect might be due to reason that both KAA and N. sativa oil acted through different mechanisms. ...
Objective: The objective of the study was to evaluate efficacy and safety Nigella sativa oil as an add-on therapy in addition to alpha-keto analog of essential amino acids in patients diabetic nephropathy (DN). Methods: The study was conducted in a tertiary care center of North India on patients of DN. It was a prospective, comparative, and open labeled study. Patients were randomly divided into two interventional groups. Group I (control) received conservative management of chronic kidney disease consisting of alpha-keto analog (600 mg tab. 3 times a day), while Group II (test) received conservative management along with alpha-keto analog and N. sativa oil (2.5 ml, per orally, once daily) for 12 weeks. Hemogram and renal function, serum electrolytes tests were done, and adverse events were recorded at baseline, 4, 8, and 12 weeks of treatment. Results: After 12 weeks of treatment, there was a marked improvement in clinical features and biochemical parameters in both the control and test groups, but it was more statistically significant in the test group as compared to control group especially in renal function (p≤0.05). Both groups showed steady improvement in the biochemical parameters as compared to their pre-treated values which were more marked in N. sativa oil supplemented group. There was a reduction in blood glucose, blood urea, serum creatinine, and 24-h total urine protein, and an increase in hemoglobin, 24-h total urine volume, and glomerular filtration rate. Conclusion: N. sativa oil supplementation along with alpha-keto analog is more efficacious and safer in delaying the progression of disease patients of DN.
... These findings may partly explain the results of a previous study demonstrating improvements in altered renal hemodynamics in response to N. sativa administration in diabetic rats. [45] The present study revealed that N. sativa lowered the mean HbA 1c level by 1.4%, which exceeds the necessary reduction previously described by the United Kingdom Prospective Diabetes Study to decrease the risk of diabetic microangiopathy. [7] Therefore, this amelioration of dermal capillary basement membrane thickening in diabetic rats treated with N. sativa extract is suggested to be a consequence of its glycemic control activity. ...
Background: Microangiopathy is a chronic diabetic complication resulting from metabolic derangements, oxidative stress, and increased pro-inflammatory cytokine production. Nigella sativa Linn. is used as an herbal medicine that exerts hypoglycemic, antilipidemic, anti-inflammatory, and antioxidant effects. Objective: To examine the effects of N. sativa extract on cutaneous microvascular changes in diabetic rats. Materials and Methods: Sprague-Dawley rats were randomly assigned into the following four groups: Untreated and N. sativa-treated normal controls and untreated and N. sativa-treated rats with streptozotocin-induced diabetes. A cold-pressed N. sativa extract was then orally administered (1000 mg/kg/day). After 8 weeks of treatment, the glucose, glycosylated hemoglobin (HbA1c), tumor necrosis factor-alpha (TNF-α), insulin levels, and lipid profile were determined in cardiac blood. Dermal capillary wall thickness was measured in tail skin sections stained with periodic acid-Schiff. Endothelial apoptosis was morphologically evaluated by hematoxylin and eosin staining. Results: Diabetes significantly reduced the circulating insulin and low-density lipoprotein levels and caused elevations in the glucose, HbA1c, and triglyceride levels, accompanied by a slight increase in total cholesterol levels and no change in the high-density lipoprotein and TNF-α levels. Capillary basement membrane thickening and a decreased capillary luminal diameter despite no evidence of endothelial cell apoptosis were also observed. N. sativa treatment of diabetic rats reduced the mean HbA1cconcentration by 1.4%, enlarged the capillary lumens, and tended to attenuate dermal capillary basement membrane thickening without affecting the lipid profile or TNF-α level. Conclusion: Our results indicate that N. sativa may be used to minimize the risk of diabetic microangiopathy, potentially due in part to its glycemic control activity.
SUMMARY
Diabetes causes dermal capillary basement membrane thickening and a decreased capillary luminal diameterNigella sativa treatment of diabetic rats enlarged the capillary lumens and tended to attenuate dermal capillary basement membrane thickeningN. sativa treatment of diabetic rats reduced the mean glycosylated hemoglobin concentration by 1.4%, which exceeds the necessary reduction previously described to decrease the risk of diabetic microangiopathy, without affecting the lipid profile or tumor necrosis factor-alpha levelN. sativa improves rat diabetic microangiopathy, potentially due in part to its glycemic control activity.
Abbreviations used: H and E: Hematoxylin and eosin, HbA1c: Glycosylated hemoglobin, HDL-C: High-density lipoprotein cholesterol, LDL-C: Low-density lipoprotein cholesterol, PAS: Periodic acid-Schiff, STZ: Streptozotocin,
TNF-α: Tumor necrosis factor-alpha.
Juraiporn Somboonwong
... These findings may partly explain the results of a previous study demonstrating improvements in altered renal hemodynamics in response to N. sativa administration in diabetic rats. [45] The present study revealed that N. sativa lowered the mean HbA 1c level by 1.4%, which exceeds the necessary reduction previously described by the United Kingdom Prospective Diabetes Study to decrease the risk of diabetic microangiopathy. [7] Therefore, this amelioration of dermal capillary basement membrane thickening in diabetic rats treated with N. sativa extract is suggested to be a consequence of its glycemic control activity. ...
... Renal hemodynamic changes and renal tubular dysfunction in TQ treated rats appeared to improve in comparison with positive control group. 23 In another study, renal injury was induced by injection of streptozotocin. Renal dysfunction was confirmed by elevated levels of urea, creatinine, nitric oxide, malondialdehyde and interleukin-6. ...
To determine the effect of thymoquinone and methotrexate on blood urea and serum creatinine in arthritic rats.
Experimental, comparative study.
Postgraduate Medical Institute, Lahore, from March to August 2013.
Thirty two female Sprague-Dawley rats were randomized into four equal groups (n=8); group A(healthy control), group B (positive control), group C (Thymoquinone treated) and group D (Methotrexate treated). Arthritis developed within two weeks after a single pristane injection. Total leukocyte count, blood urea and serum creatinine were taken at day 0, 15 and 30. While clinical score of inflammation was taken at day 0 and then on every alternate day.
Development of arthritis and renal involvement was accompanied by significant raise in total leukocyte count, clinical score of inflammation, blood urea and serum creatinine as compared to healthy control rats (group A) till day 15 (p < 0.001). From day 15 to day 30 both thymoquinone (group C) and methotrexate (group D) significantly lowered the total leukocyte count, clinical score of inflammation and improved blood urea and serum creatinine as compared to arthritic rats (group B) (p < 0.001). Methotrexate was found a bit more effective than thymoquinone.
Evaluation of results supported the beneficial effects of thymoquinone in renal injury produced by rheumatoid arthritis.
Polycystic Kidney Disease (PKD) is an inherited disorder in which the anomalous composition of the renal tubules results in the buildout of multiple cysts within the kidney. The genetic PKD mainly occurs between 30 to 40 years of age but acquired PKD can occur because of obesity, persistent high blood pressure, irregular eating patterns, and a sedentary lifestyle at any stage of life. The severe side or back pain, abdomen fullness, edema, hematuria, and weight gain are most common in both females and males. Several therapies are presented for PKD, including weight management, blood pressure control, medicaments like Tenormin, Dietary Approaches to Stop Hypertension (DASH) diet, and the use of cumin along with ajwain in place of salt. Case Summary: This case reported a 30-years-old female approached for evaluation of hypertension, severe side or back pain, and high blood pressure as well as overweight with a sedentary lifestyle. Conclusion: Cortisol hormone levels were elevated with an increased level of creatinine and urea in the blood. Tenormin and DASH diet, and cumin and ajwain were the best treatment choices for PKD patients that need additional investigation before being recommended on a long-term basis and fruitful treatment result.
The pharmacokinetics of a drug is dependent upon the coordinate work of influx transporters, enzymes and efflux transporters (i.e., transporter-enzyme interplay). The transporter–enzyme interplay may occur in liver, kidney and intestine. The influx transporters involving drug transport are organic anion transporting polypeptides (OATPs), peptide transporters (PepTs), organic anion transporters (OATs), monocarboxylate transporters (MCTs) and organic cation transporters (OCTs). The efflux transporters are P-glycoprotein (P-gp), multidrug/toxin extrusions (MATEs), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). The enzymes related to drug metabolism are mainly cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyltransferases (UGTs). Accumulating evidence has demonstrated that diabetes alters the expression and functions of CYP450s and transporters in a different manner, disordering the transporter–enzyme interplay, in turn affecting the pharmacokinetics of some drugs. We aimed to focus on (1) the imbalance of transporter-CYP450 interplay in the liver, intestine and kidney due to altered expressions of influx transporters (OATPs, OCTs, OATs, PepTs and MCT6), efflux transporters (P-gp, BCRP and MRP2) and CYP450s (CYP3As, CYP1A2, CYP2E1 and CYP2Cs) under diabetic status; (2) the net contributions of these alterations in the expression and functions of transporters and CYP450s to drug disposition, therapeutic efficacy and drug toxicity; (3) application of a physiologically-based pharmacokinetic model in transporter–enzyme interplay.
