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Kidney Health Formula

SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:

Phyllanthus Niruri Extract

Evaluation of the efficacy of Phyllanthus niruri standardized extract combined with magnesium and vitamin B6 for the treatment of patients with uncomplicated nephrolithiasis

Abstract

Introduction: The aim of our study was to assess the efficacy of Phyllanthus niruri standardized extract, combined with magnesium and B6 vitamin, used to treat uncomplicated nephrolithiasis.

Methods: We included in the present study 48 patients with uncomplicated nephrolithiasis, with the maximum calculi diameter of up to 15 mm, confirmed by non-contrast-enhanced computer tomography. Each patient followed a three-month therapeutic regimen with the above mentioned combination, with imaging assessment of the calculi after treatment.

Results: Per patient

The mean age of the patients was 48 years. The median number of calculi was 1 and the mean dimension was 5.5 mm. The stone-free status after treatment was not correlated with gender (p=0.7), side location (p=0.8) or with the number of calculi (p=0.3), but we found a correlation with the location in the upper or middle calyx (54.5% vs 13.8%, p=0.008) and with the maximum diameter (p=0.001).

Per stone

60 calculi were analyzed, 8.3% being located in the upper calyx, 36.7% in the middle and 55% in the lower one. After treatment, 40% were absent, 21.7% showed lower dimensions and 38.3% remained unchanged, with the mean reduction of 1.7 mm. We identified a cut-off value of ≤ 3 mm (AUC 0.9, CI:0.8–0.9, p<0.0001) for the prediction of stone-free status after treatment.

Conclusions: The current treatment had the highest efficacy in achieving stone-free status for patients with calculi ≤ 3 mm, located in the middle or upper calyx. A higher duration of the treatment might show improved results.

Source: Cealan A, Coman RT, Simon V, Andras I, Telecan T, Coman I, Crisan N. Evaluation of the efficacy of Phyllanthus niruri standardized extract combined with magnesium and vitamin B6 for the treatment of patients with uncomplicated nephrolithiasis. Med Pharm Rep. 2019 Apr;92(2):153-157. doi: 10.15386/mpr-1246. Epub 2019 Apr 25. PMID: 31086843; PMCID: PMC6510356.

Grape Seed Extract

Grape Seed Extract and Urolithiasis: Protection Against Oxidative Stress and Inflammation

Abstract

Background: Grape seed extract (GSE) has demonstrated various pharmacological actions. Urolithiasis is the occurrence of calculus in the renal system. The present study evaluated the anti-urolithic effect of GSE on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats.

Materials and Methods: Rats were assigned into six groups; Normal control and Normal + GSE, in which rats received standard drinking water and GSE orally daily, respectively; Urolithiatic animals received EG with AC in drinking water for 28 days; Urolithiatic animals + GSE, in which rats were administered EG with AC in drinking water and GSE 100 and 200 mg/kg orally; and Urolithiatic + cystone, where rats received EG with AC in drinking water and 750 g/kg of cystone as a standard drug orally.

Results: Urolithiatic animals showed a significant decrease in excreted magnesium and citrate and antioxidant enzymes, whereas they exhibited amplified oxalate crystal numbers, urinary excreted calcium, phosphate, oxalate ions, uric acid, intensified renal function parameters, lipid peroxidation, and inflammatory mediators. Management with GSE and cystone significantly augmented urolithiasis inhibitors (excreted magnesium and citrate) and amplified the antioxidant enzymes’ activities. GSE reduced oxalate crystal numbers and urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid excretion, lessened renal function parameters, and declined lipid peroxidation and the inflammatory mediators.

Conclusion: GSE could protect against EG-induced renal stones as evidenced by mitigated kidney dysfunction, histological alterations, and oxalate crystal formation. This action may be related to the antioxidant as well as anti-inflammatory activities of the extracts.

Source: Alomair MK, Alobaid AA, Almajed MAA, et al. Grape Seed Extract and Urolithiasis: Protection Against Oxidative Stress and Inflammation. Pharmacognosy Magazine. 2023;19(1):117-127. doi:10.1177/09731296221145069

Effects of Polyphenols from Grape Seeds on Renal Lithiasis

Abstract

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity.

Source: Grases F, Prieto RM, Fernandez-Cabot RA, Costa-Bauzá A, Tur F, Torres JJ. Effects of polyphenols from grape seeds on renal lithiasis. Oxid Med Cell Longev. 2015;2015:813737. doi: 10.1155/2015/813737. Epub 2015 Mar 25. PMID: 25883748; PMCID: PMC4389982.

Berberine HCL

Antiurolithic effect of berberine is mediated through multiple pathways

Abstract

Berberine is an isoquinoline alkaloid, occurring in nature as the main constituent of several plants with medicinal use in kidney stone disease.

This work was undertaken to evaluate its antiurolithic potential and explore the possible underlying mechanism(s). Berberine was tested in vitro for the antioxidant effect and in vivo for diuretic and antiurolithic effects on an animal model of calcium oxalate urolithiasis. Berberine exhibited concentration-dependent (50-150μg/ml) antioxidant effect against ferrous-ascorbate induced lipid peroxidation in rat kidney homogenate with potency slightly higher than the reference antioxidant, butylated hydroxytoluene. In Wistar rats, berberine (5-20mg/kg) increased urine output accompanied by increased pH and Na(+) and K(+) excretion and decreased Ca(2+) excretion, similar to hydrochlorothiazide. In an animal model of calcium oxalate urolithiasis developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water, berberine (10mg/kg) prevented as well as eliminated calcium oxalate crystal deposition in renal tubules and protected against deleterious effects of lithogenic treatment including weight loss, impaired renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted GSH and decreased antioxidant enzyme activities of the kidneys. In naïve rats, berberine (10mg/kg) increased urine volume and pH and decreased Ca(2+) excretion.

Results of this study suggest the presence of antiurolithic effects in berberine against calcium oxalate stones mediated through a combination of antioxidant, diuretic, urinary alkalinizing and hypocalciuric effects. These data invite future studies on berberine to establish its efficacy for clinical use.

Source: Bashir, S., & Gilani, A. (2011). Antiurolithic effect of berberine is mediated through multiple pathways. European journal of pharmacology, 651 1-3, 168-75.

Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: Evaluation via biochemical markers and color Doppler ultrasonography

Abstract

Diabetes and hypertension are complex and serious diseases that may ultimately lead to renal complications. Adequate control of blood glucose and blood pressure contributes to decreased renal risks, but may not be sufficient for certain patients.

The current study was undertaken to investigate the renoprotective effects of berberine as an adjuvant therapy to standard hypotensive and hypoglycemic treatment in hypertensive patients with type 2 diabetes mellitus (T2DM). In this 2-year clinical study, 69 hypertensive patients with T2DM, whose blood pressure and fasting plasma glucose (FPG) were adequately controlled by hypotensive and oral hypoglycemic agents prior to the study, were enrolled and randomly assigned into control (33 cases) and add-on (36 cases) groups. Berberine was orally administrated to the patients in the add-on group concomitantly with standard hypotensive and hypoglycemic treatment.

Baseline characteristics, including the levels of FPG, glycated hemoglobin, systolic blood pressure, diastolic blood pressure, serum creatinine, urinary albumin-to-creatine ratio (UACR), urinary osteopontin and kidney injury molecule-1 (KIM-1) were determined.

Furthermore, the oxidative stress markers malondialdehyde, urinary 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, glutathione peroxidase and total-antioxidant capacity, and the inflammatory parameters vascular adhesion molecule-1, C-reactive protein and high molecular weight-adiponectin were evaluated. In addition, ultrasonographic parameters, including peak systolic velocity, end diastolic velocity and renal arterial resistance index were determined.

After treatment, it was observed that the control and add-on treatments were able to adequately control blood pressure and blood glucose. Patients in the add-on group exhibited significant reductions in renal damage biochemical markers (UACR, urinary osteopontin and KIM-1) and improved renal hemodynamics, in addition to reduced inflammation and oxidative stress. The present results suggest that berberine is beneficial for hypertensive patients with T2DM as add-on therapy to standard hypotensive and hypoglycemic agents.

Source: Dai P, Wang J, Lin L, Zhang Y, Wang Z. Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: Evaluation via biochemical markers and color Doppler ultrasonography. Exp Ther Med. 2015 Sep;10(3):869-876. doi: 10.3892/etm.2015.2585. Epub 2015 Jun 22. PMID: 26622407; PMCID: PMC4533140.

B6 (as Pyridoxine HCL)

Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria

In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new treatment that specifically reduces oxalate production and therefore urinary oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and glyoxylate, and prevent their metabolism to oxalate. In PM treated rats, endogenous urinary oxalate levels were consistently lower and became statistically different from controls after 12 days of experiment. In ethylene glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by ~50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals, as well as in a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. These results, coupled with favorable toxicity profiles of PM in humans, show promise for the therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.

Source: Scheinman, J.I., Voziyan, P.A., Belmont, J.M., Chetyrkin, S.V., Kim, D., & Hudson, B.G. (2005). Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria. Urological Research, 33, 368-371.

Saffron

Saffron And Its Effects On Kidneys

Introduction and aims: A study which examines the efffects of saffron, the oldest medicinal plant, on kidneys.

Methods: Review of published literature on saffron and its effects on kidney diseases.

Results: Saffron is derived from the stigmas of Crocus sativus L. Flowers and its cultivation goes back to about 2300 B.C. A definite identification of saffron crocuses dates from about 1700-1600 B.C. In the 4th century B.C., the principal area of cultivation was at Corycos in Cilicia. Its name from the plant, as did the names of Krokos in Greece, Safranbolu in Turkey, and Saffron Walden in England. Saffron and its constituents are widely used as spice and medicinal plant in folk medicine. The Ebers papyrus (ca 1550 B.C.) mentions saffron as an ingredient in a cure for kidney problems (Woenig, 1886) In Unani medicine, saffron is used to reduce inflammation of enlarged liver and in infection of the bladder and kidneys. The effect of saffron extract may be related to the antioxidant properties and its reducing blood glucose level and radical scavenging effect. In ancient cultures, saffron was used to relieve kidney stones and also as an agent in improving the circulation of blood. The main compounds in saffron are crocin, picrocrocin and safranal. Since ancient times, saffron has been used as a part of religious rituals, folk medicine and cuisine. The active components in saffron have many therapeutic applications in many traditional medicines as antiseptic, antidepressant, antioxidant, digestive, and anticonvulsant. Some recent studies have shown that saffron has possible anti-carcinogenic, anti-mutagenic, and immune-modulating effects mainly resulted from antioxidant-like agents of saffron such as volatile agents (e.g., safranal), bitter principles (e.g., picrocrocin), and dye materials (e.g., crocetin and its glycoside, crocin). Saffron extract and its active constituents, crocin and picrocrocin are known to have an overall protective effect against kidney ischemia/reperfusion injury. These may be useful agents for the prevention of renal ischemia-reperfusion (IR)-induced oxidative injury in rats. Saffron and its carotenoid crocin could be potentially useful in diabetic nephropathy treatment. Safranal was found to reduce dysfunction (lowered BUN and CREA levels) and tissue damage that occur in renal tissue, by means of its both antioxidative and anti-inflammatory activities. In the light of these results, it’s suggested that safranal contributes to the development of new treatment protocols in the treatment of type 2 diabetes and its complication diabetic nephropathy.Saffron as a harmless substance can increase renal blood flow and can play the diuretic role in the diagnosis and treatment of many diseases like glomerulonephritis or localization of antigen-antibody complexes in the renal glomerulus. Antioxidative and anti-inflammatory activities and protective effects for the hydro-ethanolic extract of saffron is clear and therefore it can be used in ischemic conditions due to its diuretic effect.El daly (1998) found that daily supplement of the aqueous extract reduced the nephrotoxicity of the chemotherapy, slowing down the renal excretion.

Conclusions: It can be concluded that saffron can act as a diuretic and purifies the blood, kidney and bladder, and may regulate the BUN and sCr rate in blood.

Source: Ayla San, FO011. SAFFRON AND ITS EFFECTS ON KIDNEYS, Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, May 2018, Pages i5–i6, https://doi.org/10.1093/ndt/gfy104.FO011

Turmeric Root

Curcumin and Chronic Kidney Disease (CKD): Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase

Abstract

Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides) from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP). Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.

Source: Ghosh SS, Gehr TW, Ghosh S. Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alkaline phosphatase. Molecules. 2014 Dec 2;19(12):20139-56. doi: 10.3390/molecules191220139. PMID: 25474287; PMCID: PMC6271001.

Magnesium

Evaluation of the effects of magnesium supplement in primary and secondary preventions of nephrolithiasis: a systematic review

Introduction: The role of magnesium supplement to prevent primary and/or secondary kidney stones has not been fully determined. The aim of this study is to evaluate the effects of magnesium supplement in modifying urinary risk factors of recurrent kidney stones.

Method: We searched MEDLINE, Scopus, and Google Scholar databases on December 7, 2014 and reference lists of systematic reviews and randomized, controlled trials. Among the initial 282 articles found by our search strategy and hand searching, we found eight English-language studies were eligible for our study. Result: Magnesium supplementation could be beneficial in nephrolithiasis prevention through increasing urinary magnesium, citrate, and calcium while declining urinary oxalate. In pediatric patients, the results were more prominent and could decline urinary oxalate up to 90% of the baseline.

Conclusions: Magnesium supplementation could be beneficial, especially with potassium-citrate combination. However, due to the low number of well-designed randomized controlled trials, especially in pediatrics, the conclusions of this study need further confirmation.

Source: Azarfar, A., Esmaeili, M., Tousi, N., Naseri, M., Ghane, F., Ravanshad, Y., & Alizadeh, A. (2016). Evaluation of the effects of magnesium supplement in primary and secondary preventions of nephrolithiasis: a systematic review. Reviews in Clinical Medicine, 3, 18-22.

Black Pepper

Bioavailability enhancers of herbal origin: An overview

Abstract

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.

Source: Kesarwani K, Gupta R, Mukerjee A. Bioavailability enhancers of herbal origin: an overview. Asian Pac J Trop Biomed. 2013 Apr;3(4):253-66. doi: 10.1016/S2221-1691(13)60060-X. PMID: 23620848; PMCID: PMC3634921.

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