| Cell Research: |
| Phytomedicine. 2010 Jul;17(8-9):653-8. | | An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells.[Pubmed: 20036111 ] | Teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") have been traditionally used in Egypt as a remedy to treat kidney stones. It was the aim of our study to evaluate the effect of a Khella extract (KE) as well as the two major constituents Khellin and visnagin on renal epithelial injury using LLC-PK1 and Madin-Darby-canine kidney (MDCK) cells.
Both cell lines provide suitable model systems to study cellular processes that are possibly involved in the development of a renal stone.
METHODS AND RESULTS:
LLC-PK1 and MDCK cell lines were exposed to 300 microM oxalate (Ox) or 133 microg/cm(2) calcium oxalate monohydrate (COM) in presence or absence of 10, 50, 100 or 200 microg/mL KE. To evaluate cell damage, cell viability was assessed by determining the release of lactate dehydrogenase (LDH). KE (e.g. 100 microg/ml) significantly decreased LDH release from LLC-PK1 (Ox: 8.46+0.76%; Ox + 100 microg/ml KE: 5.41+0.94%, p<0.001) as well as MDCK cells (Ox: 30.9+6.58%; Ox+100 microg/ml KE: 17.5+2.50%, p<0.001), which indicated a prevention of cell damage. Similar effects for KE were observed in both cell lines when COM crystals were added. In LLC-PK1 cells Khellin and visnagin both decreased the % LDH release significantly in cells that were pretreated with Ox or COM crystals. However, Khellin and visnagin exhibited different responses in MDCK cells. Whereas Khellin slightly reduced the % LDH release after exposure of the cells to Ox and COM crystals, visnagin significantly decreased % LDH release only after COM crystal exposure. Overall both compounds were more active in LLC-PK1 than in MDCK cells. In summary, exposure of renal epithelial cells to Ox or COM crystals was associated with a significant release of LDH indicating cell injury.
CONCLUSIONS:
Our data demonstrate that KE as well as Khellin and visnagin could prevent renal epithelial cell damage caused by Ox and COM and could therefore play a potential role in the prevention of stone formation associated with hyperoxaluria. | | Br J Dermatol. 2003 Oct;149(4):707-17. | | KUVA (khellin plus ultraviolet A) stimulates proliferation and melanogenesis in normal human melanocytes and melanoma cells in vitro.[Pubmed: 14616361] | Khellin is a naturally occurring furochromone which, when combined with artificial ultraviolet (UV) A or solar irradiation (KUVA), is reported to repigment vitiligo skin as effectively as PUVA photochemotherapy. The exact mechanism of KUVA-induced repigmentation is unknown.
The aim of this study was to test the effect of Khellin and KUVA on proliferation and melanogenesis of normal human melanocytes and Mel-1 melanoma cells in vitro.
METHODS AND RESULTS:
Cultured normal human melanocytes, Mel-1 melanoma cells and fibroblasts were treated with Khellin, UVA and KUVA and the effect on proliferation determined by cell counting. The effect on melanogenesis was determined by a radiometric melanin formation assay. Changes in gene expression and protein synthesis were determined by Northern blot, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses.
Khellin stimulated proliferation of Mel-1 melanoma cells and melanocytes at concentrations between 1 nmol L-1 and 0.5 mmol L-1 with a peak effect at 0.01 mmol L-1 Khellin. In contrast, Khellin inhibited proliferation of fibroblasts over the entire concentration range tested. At concentrations above 0.5 mmol L-1, Khellin was cytotoxic to both melanocytic cells and fibroblasts. Exposure of Khellin-treated cells to single doses of UVA between 150 and 280 mJ cm-2 resulted in an enhanced proliferative effect. Khellin and KUVA also stimulated the melanogenic enzyme activity of pigmented cells, with the most effective treatment being 0.01 mmol L-1 Khellin with 250 mJ cm-2 UVA. Western blot, Northern blot and RT-PCR analysis revealed that these increases in melanogenic enzyme activity were not due to increases in gene expression or protein synthesis. UVA treatment resulted in an increase in enzyme glycosylation and this correlated with the increase in melanogenesis.
CONCLUSIONS:
We conclude that Khellin activated by UVA stimulates melanocyte proliferation and melanogenesis. Our results point to the possibility that current treatment regimens might be improved if reduced Khellin doses are applied and suggest that improved delivery vehicles be tested. |
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| Animal Research: |
| Urol Res. 2011 Jun;39(3):189-95. | | Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its constituents khellin and visnagin in hyperoxaluric rats.[Pubmed: 21069311] | 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 A. visnaga as well as two major constituents Khellin and visnagin could prevent crystal deposition in stone-forming rats.
METHODS AND RESULTS:
Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride 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 CaOx 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.
CONCLUSIONS:
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. |
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