Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its constituents khellin and visnagin in hyperoxaluric rats

Abstract

In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. “Khella”) are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of Ammi visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol (EG) and 1% ammonium chloride (NH4Cl) via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of calcium oxalate deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.

QUALITATIVE AND QUANTITATIVE ANALYSIS OF KHELLIN IN AMMI VISNAGA FRUITS AND PHARMACEUTICAL PREPARATIONS USING HPTLC AND HPLC

“…[3][4][5][6] Other pharmacological effects of khellin includes prevention of renal crystal deposition in hyperoxaluric rats, prevention of cell damage caused by oxalate in renal epithelial cells, and hypocholesterolemic effect. [7][8][9] A thorough literature survey has revealed that a limited number of spectrophotometric, fluorimetric, voltametric, electrophoretic, and chromatographic methods have been reported for analysis of khellin. [10][11][12][13][14][15][16] A rapid gas chromatographic assay has been used for the separation and determination of khellin in human serum.…”

Khellin and Visnagin Differentially Modulate AHR Signaling and Downstream CYP1A Activity in Human Liver Cells

“…Khellin has been extensively used by the pharmaceutical industry as basic raw material for the development of drugs such as the anti-asthmatic agent sodium cromoglycate or the widely used anti-arrhythmic drug amiodarone [18]. Recent studies identified derivatives of khellin and visnagin as suitable agents to treat different types of tumors, epileptic seizures, kidney stones and inflammatory diseases [19–22]. Due to its photosensitizing properties and lesser phototoxic side-effects compared to psoralens, khellin is also used in the photochemotherapy (khellin treatment plus ultraviolet A irradiation; KUVA) of vitiligo, a pigmentation disorder of the skin [23,24].…”

Antiurolithic and antihypertensive activities of Origanum vulgaris on urolithic rats

“…aggregation, retention and stone development (Escobar et al, 2008;Byer and Khan, 2003;Vanachayangkul et al, 2011). The antiurolithic effect of O. vulgaris was evaluated on the ethylene glycol-induced model for urolithiasis (Divakar et al, 2010;Tsai et al, 2008).…”