Targeting urinary calcium oxalate crystallization with inulin-type AOFOS from Aspidopterys obcordata Hemsl. for the management of rat urolithiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate crystals play a key role in the development and recurrence of kidney stones (also known as urolithiasis); thus, inhibiting the formation of these crystals is a central focus of urolithiasis prevention and treatment. Previously, we reported the noteworthy in vitro inhibitory effects of Aspidopterys obcordata fructo oligosaccharide (AOFOS), an active polysaccharide of the traditional Dai medicine Aspidopterys obcordata Hemsl. (commonly known as Hei Gai Guan), on the growth of calcium oxalate crystals. AIM OF THE STUDY: To investigated the effectiveness and mechanism of AOFOS in treating kidney stones. MATERIALS AND METHODS: A kidney stones rats model was developed, followed by examining AOFOS transport dynamics and effectiveness in live rats. Additionally, a correlation between the polysaccharide and calcium oxalate crystals was studied by combining crystallization experiments with density functional theory calculations. RESULTS: The results showed that the polysaccharide was transported to the urinary system. Furthermore, their accumulation was inhibited by controlling their crystallization and modulating calcium ion and oxalate properties in the urine. Consequently, this approach helped effectively prevent kidney stone formation in the rats. CONCLUSIONS: The present study emphasized the role of the polysaccharide AOFOS in modulating crystal properties and controlling crystal growth, providing valuable insights into their potential therapeutic use in managing kidney stone formation.

The anti-urolithiasis activity and safety of strangury-relieving herbs: A comparative study based on fruit fly kidney stone model.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is one of the oldest and most widespread urological diseases suffered globally. In the long history of Traditional Chinese Medicine, there're numerous herbs documented with strangury-relieving properties playing crucial roles in treating various urological disorders, including dysuria, hematuria, and renal colic, etc., which may be caused by urolithiasis. Exploring these herbs may reveal safer, more effective, and cost-efficient drugs and therapies for urolithiasis. AIM OF THE STUDY: This study aims to assess the anti-urolithiasis efficacy and safety of 46 Chinese traditional and folk herbal drugs using the fruit fly (Drosophila melanogaster) kidney stone model, in order to identify the most valuable ethnomedicinal materials. MATERIALS AND METHODS: Water extract and 50% ethanol extract of each herb were prepared respectively. 0.2% (w/w) sodium oxalate was chosen as appropriate lithogenic agent through fruit fly life span study. Male fruit-flies within three days of emergence were aged for an additional three days, then were randomly divided into experimental groups, model group and control groups (n = 20). The flies in blank control group, model group and positive control group were fed with standard food, standard food containing 0.2% sodium oxalate, standard food containing 0.2% sodium oxalate and 3% (w/w) Garcinia cambogia extract, respectively. Meanwhile, flies in the experimental groups were raised on standard food containing 0.2% sodium oxalate and 3% (w/w) herbal extract. The anti-urolithiasis capability of the extracts was evaluated using stone area ratio (the stone area divided by the area of the Malpighian tubule) and stone-clearing rate. Additionally, the 7-day mortality rate was employed as an indicator of safety. RESULTS: Out of the 46 herbs, 24 exhibited significant anti-urolithiasis effects in their water extracts. Among them, Herba Nephrolepidis, Herba Humuli, Herba Desmodii Styracifolii, Cortex Plumeriae Rubrae, and Herba Mimosae Pudicae showed us a low 7-day mortality rate of fruit-flies as well. However, only a limited number of herbal extracts (8 out of 46) showed obvious anti-urolithiasis activity in their 50% ethanol extracts. CONCLUSION: Highly potential anti-urolithiasis candidates were discovered from strangury-relieving herbs recorded in classical Traditional Chinese Medicine works, highlighting the significant value of traditional and folk ethnopharmacological knowledge.

Deciphering Multi-target Pharmacological Mechanism of Cucurbita pepo Seeds against Kidney Stones: Network Pharmacology and Molecular Docking Approach.

BACKGROUND: Urolithiasis is a prevalent condition with significant morbidity and economic implications. The economic burden associated with urolithiasis primarily stems from medical expenses. Previous literature suggests that herbal plants, including Cucurbita pepo, have lithotriptic capabilities. C. pepo is an annual, herbaceous, widely grown, and monoecious vegetative plant known for its antioxidants, fibers, and fatty acids. Recent studies on C. pepo seeds have shown therapeutic potential in reducing bladder stones and urodynamic illnesses, like kidney stones. However, the precise molecular and pharmacological mechanisms are unclear. OBJECTIVE: In this research, we employed network pharmacology and molecular docking to examine the active compounds and biological mechanisms of Cucurbita pepo against kidney stones. METHODS: Active constituents were obtained from previous studies and the IMPPAT database, with their targets predicted using Swiss target prediction. Kidney stone-associated genes were collected from DisGeNET and GeneCards. The active constituent-target-pathway network was constructed using Cytoscape, and the target protein-protein interaction network was generated using the STRING database. Gene enrichment analysis of C. pepo core targets was conducted using DAVID. Molecular docking was performed to identify potential kidney stone-fighting agents. RESULTS: The findings revealed that Cucurbita pepo contains 18 active components and has 192 potential gene targets, including AR, EGFR, ESR1, AKT1, MAPK3, SRC, and MTOR. Network analysis demonstrated that C. pepo seeds may prevent kidney stones by influencing disease-related signaling pathways. Molecular docking indicated that key kidney stone targets (mTOR, EGFR, AR, and ESR1) effectively bind with active constituents of C. pepo. CONCLUSION: These findings provide insight into the anti-kidney stone effects of Cucurbita pepo at a molecular level. In conclusion, this study contributes to understanding the potential of Cucurbita pepo in combating kidney stones and lays the foundation for further research.

Synergistic effect of doxycycline and aqueous extract of irradiated khella on structure of nanobacteria isolated from kidney stones: In vitro and in vivo studies.

Kidney stones have been associated with an increased risk of chronic kidney diseases, end-stage renal failure. This study is devoted to isolate nanobacteria from patients with active urolithiasis and investigate the in vitro and in vivo antinanobacterial activity of some antibiotics alone or in combination with extracts of irradiated herbs from certain medicinal plants. Nanobacteria were detected using scanning (SEM) and transmission (TEM) electron microscopy, protein electrophoresis (SDS-PAGE) and DNA profile. The antimicrobial susceptibility of some biofilm-producing nanobacterial isolates was evaluated. The effect of medicinal plant extracts on growth was tested. A combination treatment between the most potent extracts and antibiotics was tested on biofilm production, protein profile, release of 260 nm absorbing material, protein content, and ultrastructure of the strongest biofilm producers. In vivo study of nanobacteria and its treatment by the most potent agents was evaluated on male rats. Renal function was measured in serum; histological examination and oxidative stress parameters were determined in kidney tissues. Results showed that streptomycin, trimethoprim/sulfamethoxazole, doxycycline, and water extracts of irradiated khella at 6 kGy had antinanobacterial activity. Meanwhile, the synergistic effect of the aqueous extract of irradiated Khella and doxycycline showed higher inhibition activity on microbial growth and biofilm production. They affected dramatically the strength of its cell membrane and subsequently its ultrastructure. Moreover, these results are confirmed by ameliorations in renal function and histological alterations. It could be concluded that the combination of DO and an aqueous extract of irradiated khella has an antinephrotoxic effect against nanobacteria-induced renal toxicity.

PPARG: A Novel Target for Yellow Tea in Kidney Stone Prevention.

Kidney stones are a common urological disorder with increasing prevalence worldwide. The treatment of kidney stones mainly relies on surgical procedures or extracorporeal shock wave lithotripsy, which can effectively remove the stones but also result in some complications and recurrence. Therefore, finding a drug or natural compound that can prevent and treat kidney stones is an important research topic. In this study, we aimed to investigate the effects of yellow tea on kidney stone formation and its mechanisms of action. We induced kidney stones in rats by feeding them an ethylene glycol diet and found that yellow tea infusion reduced crystal deposits, inflammation, oxidative stress, and fibrosis in a dose-dependent manner. Through network pharmacology and quantitative structure-activity relationship modeling, we analyzed the interaction network between the compounds in yellow tea and kidney stone-related targets and verified it through in vitro and in vivo experiments. Our results showed that flavonoids in yellow tea could bind directly or indirectly to peroxisome proliferator-activated receptor gamma (PPARG) protein and affect kidney stone formation by regulating PPARG transcription factor activity. In conclusion, yellow tea may act as a potential PPARG agonist for the prevention and treatment of renal oxidative damage and fibrosis caused by kidney stones.

Hydroalcoholic Extract of Ziziphus Jujuba Leaf to Prevent Ethylene Glycol and Ammonium Chloride-Induced Kidney Stones in Male Rat: Is it Effective?

PURPOSE: This study aimed to evaluate the effect of Ziziphus jujuba (Z. jujuba) leaf hydroalcoholic extract on the prevention/treatment of kidney stones. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control, Sham (kidney stone induction (KSI) by ethylene glycol 1% + ammonium chloride 0.25% through drinking water for 28 days), Prevention groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) through gavage for 28 days), and Treatment groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) from the 15th day). On the 29th day, the rats' 24-hour urine was assessed, the animals were weighed, and blood samples were taken. Finally, after nephrectomy and weighing the kidneys, tissue sections were prepared to examine the number of calcium oxalate crystals and tissue changes. RESULTS: The results indicated a significant increase in kidney weight and index, tissue changes, and the number of calcium oxalate crystals in the Sham group compared to the control; using Z. jujuba leaf considerably reduced them in experimental groups compared to the Sham. Body weight decreased in the Sham and experimental groups (except the prevention 2 group) compared to the control, while this observed reduction was lower in all experimental groups compared to the Sham. The mean urinary calcium, uric acid, creatinine, and serum creatinine in Sham and experimental groups (except the prevention 2 group) indicated a substantial increase compared to the control and decreased significantly in all experimental groups compared to the Sham. CONCLUSION: Hydroalcoholic extract of Z. jujuba leaf is effective in the reduction of calcium oxalate crystals forming, and its most effective dose was 500mg/kg.

Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones.

Introduction: Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated. Methods: The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones. Results: Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results. Discussion: This study provides evidence that BSHS plays a critical role in anti-KS via regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.

Anti-urolithiatic effect of Cucumis melo L. var inodorous in male rats with kidney stones.

Melon seed extracts have high antioxidant activities and are effective against a variety of diseases, including kidney stones. In kidney stone model rats, the anti-urolithiatic effects of the hydro-ethanolic extract of melon seed and potassium citrate were studied and compared. After urolithiasis induction by ethylene glycol, the extract and potassium citrate were treated orally for 38 days concurrent with ethylene glycol. Then, urine and kidney sampling were done, and the urinary parameter levels were measured. The melon and potassium citrate treatments reduced the kidney index, the levels of urinary calcium and oxalate, calcium oxalate deposit numbers, the score of crystal deposits, histo-pathological damages, and the score of inflammation in the kidney sections, while elevating the urinary pH, magnesium, and citrate levels, and also the expression of the UMOD, spp1, and reg1 genes in the kidney of treated animals. The effect of potassium citrate is the same as the effect of melon in treated animals. So, their effects could be by normalizing urinary parameters, reducing crystal deposits, excreting small deposits from the kidney, reducing the chance of them being retained in the urinary tract, and elevating the expression of the UMOD, spp1, and reg1 genes, which are involved in kidney stone formation.

Identification of novel inhibitor against human phosphoethanolamine cytidylyltransferase from phytochemicals of Citrus sinensis peel extract by in vitro and in silico approach.

Kidney stone is a major global menace that demands research on nonsurgical treatment involving biological compounds for the benefit of the patients. Among the biological extracts, citric acid is traditionally used to dissolve kidney stones. The current research focuses on evaluating the in vitro anti-urolithiatic activity and in silico study of ethanolic extract of Citrus sinensis (ECS) peel against c: phosphoethanolamine cytidylyltransferase (PCYT). The diuretic activity was evaluated using in vitro model against the synthesized calcium oxalate crystals and cytotoxicity study in Madin-Darby canine kidney cell lines. The phytochemicals were identified using gas chromatography-mass spectroscopy. The interaction mechanism was studied using computational docking studies to confirm their involvement in the dissolution of calcium oxalate kidney stones. Further molecular properties, drug-likeness, ADME (absorption, distribution, metabolism, and excretion), and toxicity analysis were followed for the ligands using software tools. 5-Hydroxymethylfurfural, 2,4-di-tert-butylphenol, 2-methoxy-4-vinylphenol, 6-octen-1-ol, 3,7-dimethyl-, acetate (citronellyl acetate), 3',5'-dimethoxyacetophenone, and ethyl alpha-d-glucopyranoside showed good binding affinities against PCYT. Moreover, the docking studies showed the ligand 3',5'-dimethoxyacetophenone has the highest binding energy (-6.68 kcal/mol) for human CTP. The present investigation concludes that these compounds of C. sinensis peel extract compounds are responsible as novel inhibitors against human CTP and extend their use in the pharmaceutical drug development process.

Zn2+ regulates human oxalate metabolism by manipulating oxalate decarboxylase to treat calcium oxalate stones.

A high concentration of oxalate is associated with an increased risk of kidney calcium oxalate (CaOx) stones, and the degradation of exogenous oxalate mostly depends on oxalate-degrading enzymes from the intestinal microbiome. We found that zinc gluconate supplement to patients with CaOx kidney stones could significantly improve the abundance of oxalate metabolizing bacteria in humans through clinical experiments on patients also subjected to antibiotic treatment. The analysis of clinical samples revealed that an imbalance of Lactobacillus and oxalate decarboxylase (OxDC) was involved in the formation of CaOx kidney stones. Then, we identified that Zn2+ could be used as an external factor to improve the activity of OxDC and promote Lactobacillus in the intestinal flora, and this treatment achieved a therapeutic effect on rats with stones aggravated by antibiotics. Finally, by analyzing the three-dimensional structure of OxDC and completing in vitro experiments, we propose a model of the Zn2+-induced reduction of CaOx kidney stone symptoms in rats by increasing the metabolism of oxalate through the positive effects of Zn2+ on Lactobacillus and OxDC.

The effects of Cynodon dactylon (Poaceae family) and Dolichos biflorus (Fabaceae family) extracts on decreasing size and excretion of kidney and urinary tract stones: a randomized, double-blind controlled trial.

OBJECTIVES: Given high and growing prevalence rate of urolithiasis in most societies as well as the problems caused by this issue, it is necessary to apply more cost-effective and safer therapeutic methods, which are accessible for all the individuals worldwide. Therefore, this study aimed to investigate efficacy of herbal medicines named Cynodon dactylon and Dolichos biflorus on solving and excretion of renal and urinary tract stones in patients with urolithiasis. METHODS: This study included 96 patients with urolithiasis who were randomly allocated into three groups. The first group received the extract of D. biflorus seeds (1,600 mg), the second group received extract of C. dactylon rhizome (1,600 mg) and the third group received placebo for 21 days. In this study, we used an hydroalcoholic extract of D. biflorus and C. dactylon prepared by Soxhlet method. For each patient, the size of the stones, the amount of calcium in the urine, the number of stones excreted and their chemical substance type were measured. RESULTS: In this study, changes were observed at the significance level in the interventions groups of 1 and 2, and the placebo group in the left kidney, so that changes in size of the stone in left kidney as intergroup were significantly different in these three groups (p=0.02). The mean of changes in stone size in left kidney in the group C. dactylon was 3.78 ± 7.1 and in the group D. biflorus, it was 0.27 ± 0.6. CONCLUSIONS: A significant difference in the results of this study show that C. dactylon rhizome and D. biflorus seed extracts are able to decrease the size of the stone and can be effective on kidney stones excretion.

In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.

Alkali Citrate Content of Common Over-the-Counter and Medical Food Supplements.

Objective: Potassium citrate effectively decreases kidney stone recurrence, but it is costly and associated with side effects. While several over-the-counter supplements and medical foods purport to provide sufficient citrate to prevent recurrent stones, corroborating data on their actual citrate content is limited. Materials and Methods: Nine common nonprescription products were purchased online. Reported citrate content was obtained from packaging, promotional materials, or ingredient labels. Using a single serving of each product, actual citrate, sodium, potassium, calcium, magnesium, and oxalate content was measured using spectrophotometry and chromatography. Total alkali citrate, cost, and amounts of each component per 10 mEq of alkali citrate were also calculated. Results: Nearly all products contained more citrate than advertised, except for Litholyte® powder, Litholyte® Coffee, and Horbäach® potassium citrate. Per serving, Moonstone® powder, LithoBalance™, and KSP tabs™ contained the most citrate (means of 63.9, 33.5, and 26.9 mEq, respectively). Moonstone and LithoBalance had the greatest discrepancy between total citrate and alkali citrate (15.7 and 11.8 mEq per serving, respectively). NOW® potassium citrate was least expensive ($0.04/10 mEq alkali citrate). KSP tabs delivered the most daily sodium (mean 158 mg/10 mEq alkali citrate, Litholyte Coffee provided the most potassium (mean of 13 mEq/10 mEq alkali citrate), and Kidney COP® provided the most calcium (mean 147 mg/10 mEq alkali citrate). Conclusion: Some common over-the-counter products contain sufficient alkali to potentially promote a citraturic response; Moonstone provides the most alkali citrate, but at a higher cost than other products. Sodium, potassium, and calcium from these products must also be considered in daily consumption.

Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model.

Kidney stone disease affects nearly one in ten individuals and places a significant economic strain on global healthcare systems. Despite the high frequency of stones within the population, effective preventative strategies are lacking and disease prevalence continues to rise. Osteopontin (OPN) is a urinary protein that can inhibit the formation of renal calculi in vitro. However, the efficacy of OPN in vivo has yet to be determined. Using an established Drosophila melanogaster model of calcium oxalate urolithiasis, we demonstrated that a 16-residue synthetic OPN phosphopeptide effectively reduced stone burden in vivo. Oral supplementation with this peptide altered crystal morphology of calcium oxalate monohydrate (COM) in a similar manner to previous in vitro studies, and the presence of the OPN phosphopeptide during COM formation and adhesion significantly reduced crystal attachment to mammalian kidney cells. Altogether, this study is the first to show that an OPN phosphopeptide can directly mitigate calcium oxalate urolithiasis formation in vivo by modulating crystal morphology. These findings suggest that OPN supplementation is a promising therapeutic approach and may be clinically useful in the management of urolithiasis in humans.

Over-the-Counter Alkali Agents to Raise Urine pH and Citrate Excretion: A Prospective Crossover Study in Healthy Adults.

OBJECTIVE: To assess the effect of 2 over-the-counter alkalizing agents on 24 hour urinary parameters. MATERIALS AND METHODS: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24 hour urinalysis with a 4 day diet inventory. Participants then maintained the same diet on either LithoLyte (20 mEq 2 times per day) or KSPtabs (1 tablet 2 times per day) and submitted another 24 hour urinalysis. The process was repeated with the other supplement. Urinary alkali parameters were compared to baseline, and side effects were elicited with a questionnaire. RESULTS: LithoLyte intake resulted in a non-significant increase in citrate (597-758 mg/day, P =.058, an increase in urine pH (6.46-6.66, P =.028), and a decrease in urine ammonium (41-36 mmol/day, P =.005) compared to baseline. KSPtabs resulted in an increase in citrate (597-797 mg/day, P =.037) and urine pH (6.46-6.86, P =.037), with a non-significant decrease in ammonium (41-34 mmol/day, P =.059). No significant differences were seen comparing urinary analytes between LithoLyte and KSPtabs. With Litholyte, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabs, rates were 60%, 20%, 10%, and 10%, respectively. CONCLUSION: In healthy participants without a history of kidney stones, LithoLyte and KSPtabs are effective over-the-counter alkali supplements, with a similar side effect profile to prescription potassium citrate.

Screening out key compounds of Glechomae Herba for antiurolithic activity and quality control based on spectrum-effect relationships coupled with UPLC-QDA.

Glechomae Herba (GH) has been widely used in the treatment of urolithiasis, especially kidney stones, in China and Southeast Asia. Pharmacological studies have suggested that the antioxidant property of GH contributes to its anticalculus effect. CaSR is one of the main locations of kidney stones, and the mechanism of action of CaSR inhibitors in the treatment of kidney stones is similar to that of GH. However, until now, the antiurolithic chemical compounds in GH and their interaction with CaSR remain unknown. In our study, we revealed the interaction between the active compounds in GH and the active compounds in CaSR inhibitors by using spectrum-effect relationship analysis, pharmacodynamics, and molecular docking techniques. The results showed ten common peaks from the fingerprints of GH extracts from different regions. Pharmacological experiments showed that GH could significantly treat renal tissue lesions. Chlorogenic acid (CA), rosmarinic acid (RA), P5, luteolin, apigenin, and P9 were screened after the analysis of spectrum-effect relationships. In vitro validation experiments showed that all the screened compounds had inhibitory effects on the development of kidney stones in our model. The molecular docking results showed that the above compounds could be docked with CaSR in a natural state, and the docking score was less than 7. This work constructs a general model for the combination of UPLC-QDA and antiurolithic drugs, studies the spectrum-effect relationship of GH, and provides a new possibility for the development of new antiurolithic drugs.

Insights into the cytoprotective potential of Bergenia ligulata against oxalate-induced oxidative stress and epithelial-mesenchymal transition (EMT) via TGFß1/p38MAPK pathway in human renal epithelial cells.

Oxalate exposure to human renal epithelial cells triggers a vicious cycle of oxidative stress leading to cellular injury and deposition of calcium oxalate crystals on the injured cells. This results in further oxidative damage causing inflammation and loss of cell-cell adhesion factors, ultimately leading to irreparable kidney damage. However, these events can be attenuated or prevented by plants rich in antioxidants used in the traditional system of medicine for treatment of kidney stones. To delineate the mechanism by which Bergenia ligulata extract exerts its cytoprotective role in oxalate-induced injury we designed this study. Our results revealed that oxalate-injured HK2 cells cotreated with ethanolic extract of Bergenia ligulata displayed increased viability, reduced oxidative stress due to lowered production of intracellular reactive oxygen species (ROS) and decreased apoptosis. We also observed lowered markers of inflammation, along with increased expression of epithelial marker E-cadherin and decreased expression of mesenchymal markers Vimentin, F-actin, Transforming growth factor beta 1 (TGF-ß1) and EMT-related proteins in renal tubular epithelial cells through immunocytochemistry, real-time PCR and western blotting. Our findings collectively suggest that by reducing oxidative stress, modulating crystal structure and preventing crystal-cell adhesion, B. ligulata inhibits the EMT pathway by downregulating the various mediators and thereby exerts its cytoprotective effect.

Causes and prevention of kidney stones: separating myth from fact.

Despite high-level evidence supporting the use of pharmacotherapy therapy for the prevention of kidney stones, adherence to medications is often poor because of side-effects, inconvenience and cost. Furthermore, with a desire for more 'natural' products, patients seek dietary and herbal remedies over pharmacotherapy. However, patients are often unaware of the potential side-effects, lack of evidence and cost of these remedies. Therefore, in the present review we examine the evidence for a few of the commonly espoused non-prescription agents or dietary recommendations that are thought to prevent stone formation, including lemonade, fish oil (omega fatty acids), Phyllanthus niruri and the Dietary Approaches to Stop Hypertension (DASH) diet. While the present review includes only a few of the stone-modulating recommendations available to the lay community, we focussed on these four due to their prevalent use. Our goal is not to only dispel commonly held notions about stone disease, but also to highlight the lack of high-level evidence for many commonly utilised treatments.

Therapeutic and Preventive Effects of Aqueous Extract of Date Palm (Phoenix dactylifera L.) Pits on Ethylene Glycol-Induced Kidney Calculi in Rats.

INTRODUCTION: Urinary tract stones are one of the most common diseases in the urinary tract. Lack of kidney stone treatment causes irreparable damages to the kidneys, which has many harmful effects. Date palm pits are recommended in traditional medicine as an effective drug in the treatment of kidney stones. The aim of this study was to investigate the effect of aqueous extract of date palm pits on kidney stones induced by ethylene glycol in male rats. METHODS: In this study, 40 rats were classified into five groups (n = 8), including the healthy group receiving normal water, the negative control group, the therapeutic groups with doses of 150 mg/kg and 300 mg/kg, and the prevention group with a dose of 300 mg/kg. In order to induce kidney stones, ethylene glycolated water (1%) was used as drinking water in the studied groups. Blood and urine of rats were collected on days 14 and 28 of the study to assess urinary parameters of calcium, creatinine, uric acid and phosphorus, and serum parameters of blood urea nitrogen, creatinine, uric acid, calcium, and phosphorus. Also, the kidneys of rats were removed from the body on day 28 of the study and were given to a pathologist for examination. RESULTS: Results of serum parameters shows that the use of date palm pits extract in the treatment and prevention groups with a dose of 300 mg/kg significantly (P < .05) has reduced the levels of blood urea nitrogen, uric acid, calcium, creatinine and phosphorus. Also, the results of urinary parameters show that the use of the extract caused a significant decrease (P < .05) in creatinine, uric acid and calcium in the prevention group and a significant decrease (P < .05) in creatinine and uric acid in the therapeutic group with a dose of 300 mg/kg. Pathological results show a decrease in the number and size of calcium oxalate crystals in renal tubules in the treatment and prevention groups in a dose-dependent manner. CONCLUSION: The results of this study showed that the use of aqueous extract of date palm pits has been effective in the treatment and prevention of kidney stones induced by ethylene glycol in rats.

Evaluation of Diuretic and Antioxidant Properties in Aqueous Bark and Fruit Extracts of Pine.

OBJECTIVE: The present study has been carried out to evaluate the diuretic and antioxidant properties of pine herb in an animal model. MATERIALS AND METHODS: 45 adult male rats were randomly divided into nine groups including: groups I (the negative control), groups II (positive control, furosemide 10 mg/kg), groups III to VIII (treatment groups received 100, 200, 400 mg/kg of the aqueous extracts of bark and fruit) and group IX received the combination of aqueous extract of bark (100 mg/kg) and the fruit (100 mg/kg). The urine output, glomerular filtration rate (GFR), electrolytes, urea, and creatinine levels were evaluated. Furthermore, the phenolic content and antioxidant activity of both extracts were also assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and Folin-Ciocalteu methods. RESULTS: The aqueous extracts of the pine bark and fruit increased the urinary output in a dosedependent manner. The combination of the two extracts compared to the other extracts alone significantly increased the serum potassium level. This study also showed each extract increase creatinine clearance in a dose-dependent manner (p<0.01 and p<0.05). The increase of GFR in the combination group was not significant. The current data showed a significant increase in the total phenolic content in pine bark extract in compared with the fruit extract. CONCLUSION: The pine bark and fruit can be useful in the prevention and treatment of kidney stones due to the high diuretic properties and antioxidant activity.