Propolis and its therapeutic effects on renal diseases: A review.

Propolis is produced by bees using a mixture of bees wax and saliva. It contains several bioactive compounds that mainly induce anti-oxidant and anti-inflammatory effects. In this review, we aimed to investigate the effects of propolis on kidney diseases. We used "Kidney", "Disease", "Propolis", "Renal", "Constituent", "Mechanism", "Infection", and other related keywords as the main keywords to search for works published before July 2023 in Google scholar, Scopus, and Pubmed databases. The search terms were selected according to Medical Subject Headings (MeSH). This review showed that propolis affects renal disorders with inflammatory and oxidative etiology due to its bioactive compounds, mainly flavonoids and polyphenols. There have been few studies on the effects of propolis on kidney diseases; nevertheless, the available studies are integrated in this review. Overall, propolis appears to be effective against several renal diseases through influencing mechanisms such as apoptosis, oxidative balance, and inflammation.

Effects of Dichloromethane and N-Butanol Fractions of Nigella sativa on ACHN and GP-293 Cell Line Morphology, Viability, and Apoptosis.

Background: Renal cell carcinoma (RCC) is among the top death-causing cancers. Medicinal herbs can also have beneficial effects on RCC treatment. In this project, we aimed to study the antitumor effect of dichloromethane and N-butanol fractions of hydroalcoholic extract of Nigella sativa (N. sativa) on the morphology, viability, and apoptosis of ACHN (human renal adenocarcinoma) and GP-293 (normal renal epithelial) cell lines. Materials and Methods: In this experimental study, N-butanol and dichloromethane fractions of N. sativa were obtained, and ACHN and GP293 cell lines were treated with various concentrations of dichloromethane (0-100 µg/mL) and N-butanol (0-12.5 µg/mL) fractions for 24, 48, and 72 hours. Then, morphological changes, viability, and apoptosis were investigated. Results: Our results indicated that dichloromethane and N-butanol fractions cause morphological changes and significant decreases in the percentage of live cells in the ACHN cell line, in a dose- and time-dependent manner. In the GP-293 cell line, however, a lower toxicity was observed in comparison with that found for ACHN. The results of flow cytometry showed an apoptotic effect of dichloromethane and N-butanol fractions on the ACHN cell line but a higher rate of apoptosis induction for the total extract compared to the two fractions in the renal cancer cell line compared to the normal cell line. Conclusion: Our findings demonstrated that these two fractions of N. sativa induce inhibitory effects on the ACHN cell line morphology and viability. These effects were lower than those induced by the total extract. In addition, the two fractions caused more marked effects in the renal cancer cell line compared with the GP-293 cell line.

Protective effects of Portulaca oleracea and vitamin E on cardiovascular parameters in rats with subclinical hyperthyroidism.

INTRODUCTION: Subclinical hyperthyroidism (SHT) is an endocrine disorder that is associated with abnormalities in heart structure and function. Oxidative stress plays an important role in the pathophysiology of cardiac disorders caused by SHT. Portulaca oleracea (P. Oleracea) is a herbaceous plant with many pharmacologic effects including antioxidant, and anti-inflammatory properties. In the present study, the effects of Portulaca oleracea and vitamin E on the biochemical, hemodynamic, and functional parameters of the cardiac tissue was studied in rats with subclinical hyperthyroidism. METHODS: Fifty-six male rats were divided into seven groups: 1-Control group: daily injection of saline, 2-SHT group: daily injection of levothyroxine sodium (LS) (20 µg/kg), 3- T4+Po groups were given LS and P. oleracea (100, 200, and 400 mg/kg in drinking water), 4- the T4+vit E groups received LS and a daily injection of vitamin E (100 and 200 mg/kg). Cardiac index, systolic blood pressure (SBP), also malondialdehyde and total thiol levels were measured in cardiac tissue. RESULTS: SBP and maximum dP/dt were significantly increased and minimum dP/dt was significantly decreased in SHT group. In P. oleracea groups, maximum dP/dt were significantly reduced and minimum dP/dt was increased. Malondialdehyde levels and cardiac index in groups receiving vitamin E and P. oleracea were significantly decreased. Maximum dP/dt was decreased in the group receiving LS+vitamin E. Minimum dP/dt was significantly higher in group received LS+ vitamin E. CONCLUSION: This study showed that Portulaca oleracea has a positive effect on cardiac dysfunction caused by subclinical hyperthyroidism.

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats.

OBJECTIVES: Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. METHODS: The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. RESULTS: The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). CONCLUSIONS: Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.

Kidney dysfunction and oxidative stress in doxorubicin-induced nephrotic rat: Protective role of sesame oil.

Doxorubicin (DOX) is an antineoplastic agent which it's clinical use has been limited due to its major side effects including cardiotoxicity and nephrotic syndrome. Sesame oil (SO) is an important edible oil with many pharmacologic effects. The aim of the present study was to investigate the effect of SO against DOX-induced nephropathy in the rat. In this study, two doses of SO (3 and 6 mL/kg) were administrated orally for six consecutive weeks and DOX (mg/kg) was intravenously injected on the 4th day of the experiment. Blood and urine samples were collected on days 1, 14, 30, and 42 for subsequent measurement of biochemical parameters. The left kidneys were removed for subsequent assessment of total thiol content, malondialdehyde (MDA) concentration, and renal activities of catalase and superoxide dismutase enzymes. DOX caused significant proteinuria, hypoalbuminemia, and hyperlipidemia compared to control group. Significant decrease in antioxidant enzyme activities and total thiol contents and significant increase in MDA levels were also observed following DOX injection when compared to control group. Oral administration of SO significantly reversed DOX-induced proteinuria, hypoalbuminemia, and hyperlipidemia compared to DOX group. Furthermore, compared to DOX group, SO significantly increased total thiols content. MDA concentration significantly decreased following SO administration when compared to DOX group. The current study suggests that SO is able to improve kidney function as well as kidney tissue oxidative damage in DOX-induced nephrotic the rat.

The Role of Chemokines in Cardiovascular Diseases and the Therapeutic Effect of Curcumin on CXCL8 and CCL2 as Pathological Chemokines in Atherosclerosis.

Curcumin, as a vegetative flavonoid, has a protective and therapeutic role in various adverse states such as oxidative stress and inflammation. Remedial properties of this component have been reported in the different chronic diseases including cancers (myeloma, pancreatic, breast, colorectal), vitiligo, psoriasis, neuropathic pains, inflammatory disorders (osteoarthritis, uveitis, ulcerative colitis, Alzheimer), cardiovascular conditions, and diabetes.Cardiovascular disorders include atherosclerosis and various manifestations of atherosclerosis such as stroke, and myocardial infarction (MI) is the leading cause of mortality globally. Studies have shown varying expressions of inflammatory and non-inflammatory chemokines and chemokine receptors in cardiovascular disease, which have been highlighted first in this review. The alteration in chemokines secretion and chemokine receptors has an essential role in the pathophysiology of cardiovascular disease. Chemokines as cytokines with low molecular weight (8-12 kDa) mediate white blood cell (WBC) chemotactic reactions, vascular cell migration, and proliferation that induce endothelial dysfunction, atherogenesis, and cardiac hypertrophy.Several studies reported that curcumin could be advantageous in the attenuation of cardiovascular diseases via anti-inflammatory effects and redress of chemokine secretion and chemokine receptors. We present these studies with a focus on two chemokines: CXCL8 (IL-8) and CCL2 (chemoattractant protein 1 or MCP-1). Future research will further elucidate the precise potential of curcumin on chemokines in the adjustment of cardiovascular system activity or curcumin chemokine-based therapies.

The effects of the combination of Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata on learning and memory deficit and oxidative damage in brain tissue of hypothyroid rats.

In the present study, the impact of a combination of four memory-enhancer herbs on cognitive impairment and brain tissue oxidative damage due to hypothyroidism was evaluated. Propylthiouracil (PTU; 0.05%) was administrated in drinking water. Rats were treated with a combination of four herbal products (Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata) mixed with honey at two doses (640 and 1,280 mg/kg) or donepezil (0.5 mg/kg), for 6 weeks. Memory performance on the Morris water maze (MWM) and avoidance behavior in passive avoidance was impaired by hypothyroidism, and brain tissue oxidative damage occurred. Herbal combination and donepezil significantly improved memory impairment, reduced malondialdehyde concentration, and nitric oxide metabolites while increased the thiol contents and catalase and superoxide dismutase enzymes activity in the brain. Our findings suggest that the mixture of herbal products improves learning and memory deficits caused by hypothyroidism, probably by reducing the brain tissue oxidative damage. PRACTICAL APPLICATIONS: Learning and memory impairment is a common feature of thyroid hormones deficiency. Several studies are showing that hypothyroidism in juvenile and mature rats induces significant cognitive impairment. Likewise, in humans, a close relationship between thyroid hormone deficiency and cognitive impairment has been reported. We used a mixture of herbal products, including Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata, to treat hypothyroidism-induced memory impairment. All these herbs are widely used as a food additive across the world. In Iranian traditional medicine, this herbal combination traditionally used to treat cognitive impairments. Numerous studies have indicated that these herbs show neuroprotective and memory-enhancing properties. Our finding indicated that a traditionally used herbal combination could potentially use as a treatment of cognitive impairment induced by thyroid hormone deficiency.

Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)-ß1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF-ß1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01-p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001-p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO-induced kidney fibrosis and dysfunction.

Plantago major protects against cisplatin-induced renal dysfunction and tissue damage in rats.

The aim of the present study was to determine the effect of Plantago major (P. major) on cisplatin-induced kidney injury in the rat. Cisplatin was injected on the 6th day of the experiment. Animals were treated with P. major extract (300, 600, and 1200 mg/kg) and Vitamin E for five days before and two weeks after cisplatin administration. Cisplatin caused a significant decrease in glomerular filtration rate (GFR), urine osmolarity, and urinary excretion rate of potassium, but significant increase in the kidney index and histological damage compared with the control group. Administration of Vitamin E and P. major (300 and 600 mg/kg) significantly increased GFR compared to cisplatin group. Furthermore, urine osmolarity in Vitamin E and P. major (600 mg/kg) groups were significantly elevated compared to the cisplatin group. P. major (600 mg/kg) significantly increased the urinary excretion rate of potassium compared with cisplatin group. Furthermore, all doses of P. major and Vitamin E significantly attenuated the percentage of kidney tissue damage compared to the cisplatin group. However, only P. major (600 mg/kg) and Vitamin E treated rats showed a significant reduction in the kidney index. This study revealed that P. major extract in a dose-dependent manner provides protection against renal damage induced by cisplatin.

Nigella sativa extract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) is a well-established experimental model to evaluate renal interstitial fibrosis. Current study is aimed to investigate the effects of Nigella sativa (NS) extract and renin-angiotensin system (RAS) blockade against kidney damage following UUO in rats. In this study, the rats received intraperitoneal injection of losartan (15 mg/kg), captopril (30 mg/kg), and two doses of NS extract (200 and 400 mg/kg) for 18 consecutive days. At the fourth day of the experiment, laparotomy was performed, and the left ureter was ligated. Sham-operated animals received saline as vehicle, and laparotomy without ureteral ligation was done. UUO was associated with significant increase in the expression of renal angiotensin II and monocyte chemoattractant protein-1, concentration of malondialdehyde and tumor necrosis factor-α, and the number of apoptotic cells when compared with sham group. Renal total thiol content and the activity of antioxidant enzymes were significantly reduced as compared with the sham group. However, treatment of obstructed rats with losartan, captopril, and NS extract significantly improved these renal impairments when compared with UUO group. Thus, NS extract, a potent antioxidant and anti-inflammatory herb, is a therapeutic agent to treat the UUO-induced kidney damage comparable with the well-known RAS inhibitors captopril and losartan.

Protection Against Doxorubicin-induced Nephropathy by Plantago major in Rat.

INTRODUCTION: Nephropathy is an important side effect of doxorubicin. The aim of the current study was to investigate the protective effect of Plantago major extract against doxorubicin-induced functional and histological damage in rat's kidney. MATERIALS AND METHODS: Sixty Albino rats were randomly divided into 6 groups. Doxorubicin, 5 mg/kg, was injected intravenously on the 7th day of the study. Animals were treated with dexamethasone, 0.9 mg/kg, vitamin E, 100 mg/kg, and P major extract, 600 mg/kg and 1200 mg/kg, for 7 days before and 4 weeks after doxorubicin administration. Glomerular filtration rate, urea clearance, and urine glucose concentration were determined on the 1st day and 1, 2, 3 and 4 weeks after doxorubicin injection. Histological changes were also examined and the end of the study. RESULTS: Doxorubicin caused significant decreases in glomerular filtration rate and urea clearance and significant glycosuria and kidney damage. Urea clearance in the rats treated with P major showed no significant change between different days of the experiment. Administration of dexamethasone, vitamin E, and low- and high-dose P major significantly improved the glycosuria and kidney tissue damage. CONCLUSIONS: These findings suggested that hydroalcoholic extract of P major protected renal tissue against doxorubicin-induced nephropathy. The protective effects of P major on renal lesions associated with doxorubicin may be due to its antioxidant and anti-inflammatory actions.

Renoprotective effect of Nigella sativa against cisplatin-induced nephrotoxicity and oxidative stress in rat.

Cisplatin is one of the important antineoplastic drugs. Its clinical use has been restricted due to severe kidney toxicity. Nigella sativa (N. sativa) is an herbaceous plant with many pharmacologic effects. In the present study, we evaluated the protective effects of aqueous-ethanolic extract of N. sativa and Vitamin E on cisplatin-induced nephrotoxicity in rats. Eighty male rats were divided into eight groups: control, cisplatin (6 mg/kg; ip), preventive Vitamin E (100 mg/kg), preventive N. sativa (100,200 mg/kg), preventive + treatment Vitamin E, and preventive + treatment N. sativa (100, 200 mg/kg). Duration of this study was 11 days and cisplatin was injected on the 6th day of the experiment. Tissue damage in all groups that received N. sativa extract and Vitamin E showed a significant improvement compared with the cisplatin group. In addition, serum and tissue total thiol content in preventive and preventive + treatment N. sativa groups showed significant increase compared with cisplatin group. There was no significant difference in serum malondialdehyde concentration of the control rats compared with the preventive and preventive + treatment N. sativa groups. N. sativa extract and viamin E improved the pathology and oxidative stress in the rat kidney. However, more studies are needed to determine the mechanism of action of N. sativa on cisplatin-induced kidney toxicity.

Mixed hydroalcoholic extracts of Nigella sativa and Curcuma longa improves adriamycin-induced renal injury in rat.

Extracts of both Curcuma longa (CL) and Nigella sativa extract (NS) are reported to have protective effects on renal damage. In this study, we investigated the protective effect of a combination of NS and CL on Adriamycin (ADR)-induced renal damage. Forty eight rats were divided into six groups as: Control (CO), ADR, Vitamin C + ADR, CL + ADR, NS +ADR, and CL + NS + ADR. ADR was injected intravenously on the 7th day of the study. 24-hour urine and orbital blood samples were collected on day 0, 48 hr after ADR injection and at the end of weeks 2, 3, 4, and on the 35th day. Glomerular filtration rate (GFR) was calculated on each sample, and on the 35th day, renal index and histological changes were also evaluated. In the ADR-treated rats, significant renal pathological changes were demonstrated compared to CO group. The renal index and urine protein excretion significantly increased, and serum albumin and GFR in the ADR-treated rats were significantly decreased compared to CO group. In NS + ADR group, the serum albumin significantly decreased compared to ADR group. In CL + NS + ADR group, the urine protein excretion was lower than ADR group, and serum albumin concentration was significantly higher than ADR group. In addition, in CL + ADR and NS + ADR groups also, the urine protein was significantly lower compared to ADR group. This study shows that the mixed extracts of N. sativa and CL have positive synergistic effects on renal damage in nephropathy induced by ADR in rats.

Drug-induced Nephrotoxicity and Medicinal Plants.

Drug-induced nephrotoxicity is one of the most common causes of acute kidney injury. There are various agents that exert nephrotoxic effects through different pathogenic mechanisms. Aminoglycoside antibiotics, chemotherapeutic agents, radiocontrast media, and nonsteroidal anti-inflammatory drugs are among common nephrotoxic agents. In recent years, natural compounds are being increasingly used in the treatment of kidney diseases. Given many reports available on the curative effects of a variety of medicinal plants against drug-associated nephrotoxicity, we aimed to review the protective effects of medicinal plants on certain nephrotoxic drugs.

Renoprotective Effect of Plantago Major Against Nephrotoxicity and Oxidative Stress Induced by Cisplatin.

INTRODUCTION: The aim of this study was to investigate the possible renoprotective effect of Plantago major extract against cisplatin-induced nephrotoxicity in rats. MATERIALS AND METHODS: Rats were divided into 6 groups. The first group was the control, group 2 was treated with cisplatin (7 mg/kg, single dose), and groups 3 to 6 received cisplatin with vitamin E (100 mg/kg) and Plantago major  extract at doses of 300 mg/kg, 600 mg/kg, and 1200 mg/kg, for 20 days. RESULTS: On day12, serum concentration of urea, creatinine, and potassium significantly increased and sodium concentration significantly decreased in the cisplatin group compared with the control rats. However, serum creatinine, urea, and potassium concentrations were significantly lower in all of the Plantago major groups compared to the cisplatin group. Also, there was a significant elevation in serum sodium concentration in the Plantago major 600 mg/kg group compared to the cisplatin group on day12. Injection of cisplatin caused a significant elevation in malondialdehyde concentration but a significant decrease in catalase activity and total thiol content compared to the control group. Plantago major extract at 1200 mg/kg significantly improved malondialdehyde concentration and total thiol content compared to the cisplatin group. Catalase activity with Plantago major significantly increased at all doses compared to the cisplatin group. CONCLUSIONS: The current study suggests that Plantago major extract and vitamin E are able to improve kidney function as well as oxidative stress in cisplatin-induced renal toxicity in the rat.