In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.
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.
In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major β-carboline alkaloids of P. harmala were investigated.
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).
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.
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.
Rashid S
，Sameti M
，Alqarni MH
，Abdel Bar FM
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Evaluation of anti-urolithiatic and diuretic activities of watermelon (Citrullus lanatus) using in vivo and in vitro experiments.
Traditionally, Citrullus lanatus is known to have protective properties in kidney diseases and for having the ability to clear urine. Current study aims to validate the traditional uses of C. lanatus by evaluation of anti-urolithiatic and diuretic activities using in vivo and in vitro experiments. Male Wistar rats were used for in vivo anti-urolithiatic and diuretic activities. Supersaturated solution of calcium and oxalate was used for in vitro crystallization study. Hematoxylin & eosin staining was used for histopathological evaluation of kidney. In the in vivo rat model of urolithiasis, the pulp extract reduced calcium oxalate (CaOX) crystal count in both kidney and urine. The pulp extract also increased the urinary pH and output, and prevented the weight loss. Serum analysis showed elevation in creatinine clearance and reduction in urea and creatinine levels. Urinary analysis demonstrated that pulp extract restored altered phosphate, calcium, oxalate, and citrate levels. In the in vivo rat model of diuresis; the pulp extract produced diuresis, reduced serum chloride levels, and elevated urinary sodium and chloride levels. In the in vitro crystallization experiment, pulp extract inhibited the aggregation phase. Seed extract failed to show any convincing results. GC-MS analysis revealed the presence of steroids and alkanes as the major constituents of pulp extract, which might be responsible for anti-urolithiatic activity; however, further studies are required for isolation and identification of active constituents. Current study validated the traditional uses of watermelon and demonstrated that pulp extract possessed significant anti-urolithiatic and diuretic activities.
Siddiqui WA
，Shahzad M
，Shabbir A
，Ahmad A
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Morin hydrate mitigates calcium oxalate urolithiasis by inhibiting oxalate synthesis and modulating crystal formation.
Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones.
Ponugoti M
，Guntupalli C
，Malothu N
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