Atmani F, Farell G, Lieske JC. Extract from Herniaria hirsuta coats calcium oxalate monohydrate crystals and blocks their adhesion to renal epithelial cells. J Urol. 2004 Oct;172(4 Pt 1):1510-4. Abstract: PURPOSE: The interaction of calcium oxalate crystals with renal epithelial cells is a critical event in kidney stone formation. In this study we assessed the effect of aqueous extract from Herniaria hirsuta on the adhesion of calcium oxalate monohydrate (COM) crystals to cultured renal cells.
MATERIALS AND METHODS: Madin Darby canine kidney cells were used as a model for studying the adhesion of radioactive COM crystals in the presence and absence of plant extract. RESULTS: COM crystal binding to cells was inhibited by extract in a concentration dependent manner. Prior exposure of crystals but not cells to extract blocked crystal binding, suggesting that plant molecules can coat and exert their effect at the crystal surface. Crystal attachment appeared related to
membrane fluidity since crystal adhesion increased at higher vs lower temperatures (37C vs 0C) and Herniaria extract altered crystal adhesion only under conditions of increased fluidity (increased temperature). Extract also displaced a significant portion of prebound crystals without apparent effects on cell function or the morphology of preexisting calcium oxalate crystals. Herniaria extract exerted no adverse or toxic effect on cells, which proliferated normally in its presence even at relatively high concentrations. CONCLUSIONS: Our current data suggest a mechanism whereby Herniaria hirsuta extract used in traditional medicine might prevent and possibly eliminate preexisting kidney stones. Further characterization of the active compound(s) could identify a new candidate drug for patients with nephrolithiasis.
Ivorra M.D., Valiente M., Martínez S., Madrero Y., M.A. Noguera, Cassels B.K., Sobarzo E.M., D’Ocon P. 8-NH2-Boldine, an Antagonist of alpha1A and alpha1B Adrenoceptors without Affinity for the alpha1D Subtype: Structural Requirements for Aporphines at alpha1-Adrenoceptor Subtypes. Planta Med. 2005 Oct; 71 (10): 897-903 16254819 (P,S,G,E,B,D). Abstract: Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human alpha (1A), alpha (1B) and alpha (1D) adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each alpha (1)AR subtype. All the compounds tested competed for [(125)I]-HEAT binding with steep andmonophasic curves. The most interesting compound was 8-NH (2)-boldine, which retains the selective affinity for alpha(1A)-AR (pKi = 6.37 +/- 0.21) vs. alpha(1B)- AR (pKi = 5.53 +/- 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for alpha(1D)-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cortex confirms the results obtained for human cloned alpha (1)-AR subtypes. The compounds selective for the alpha (1A) subtype discriminate two binding sites in rat cerebral cortex confirming a mixed population of alpha (1A)- and alpha (1B)-AR in this tissue. All compounds are more selective as inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. A close relationship was found between affinities obtained for cloned alpha (1A)-AR and inhibitory potencies on noradrenaline-induced contraction or inositol phosphate accumulation in tail artery, confirming that there is a homogeneous functional population of alpha(1A)-AR in this vessel. On the contrary, a poor correlation seems to exist between the affinity of 8-NH (2)-boldine for cloned alpha (1D)-AR and its potency as an inhibitor of noradrenalineinduced contraction or inositol phosphate accumulation in rat aorta, which confirms that a heterogeneous population of alpha (1)-AR mediates the adrenergic response in this vessel.
Atmani F, Khan SR. 2000. Effects of an extract from Herniaria hirsuta on calcium oxalate crystallization in vitro. BJU Int. 2000 Apr; 85(6): 621-5. Abstract: OBJECTIVE: To evaluate the effectiveness of an extract obtained from Herniaria hirsuta on calcium oxalate crystallization in vitro. Materials and methods An extract was prepared from H. hirsuta at different concentrations (0.0625-1mg/mL). Crystallization was induced in whole normal human urine samples in the absence or presence of the extract. Crystals generated in the urine were harvested and analysed by scanning electron microscopy. The nucleation and aggregation of calcium oxalate crystals were measured separately using spectrophotometric methods. The nucleation rate was followed at 620 nm after mixing calcium chloride and sodium oxalate solution at 37 degrees C, with stirring. The induction time in the presence of herb extract was compared with that of the control. The aggregation rate was also followed at 620 nm in a buffered solution containing calcium oxalate monohydrate crystals after stopping the stirring. The rate was evaluated by comparing the slope of turbidity in the presence of the extract with that of the control. RESULTS: The herb extract promoted the precipitation of calcium oxalate particles in whole urine. SEM showed that there were more crystals with increasing concentration of extract but that they were proportionally smaller. Moreover, the presence of herb extract favoured the formation of calcium oxalate dihydrate rather than monohydrate crystals. The extract inhibited calcium oxalate crystal aggregation. In an independent experiment, the herb extract was dialysed and filtered before inducing crystallization, to eliminate any fibrous particles and oxalate. The treated herb extract promoted more crystallization, especially at high concentrations. CONCLUSION: An extract of H. hirsuta promoted the nucleation of calcium oxalate crystals, increasing their number but decreasing their size. It also promoted the formation of calcium oxalate dihydrate crystals, despite the presence of calcium oxalate monohydrate particles. The extract may contain substances that inhibit calcium oxalate crystal aggregation. These properties of H. hirsuta might be beneficial in preventing kidney stone formation.
Atmani F, Slimani Y, Mimouni M, Hacht B. Prophylaxis of calcium oxalate stones by Herniaria hirsuta on experimentally induced nephrolithiasis in rats. BJU Int. 2003 Jul;92(1):137-40. Abstract: OBJECTIVE: To evaluate the prophylactic potential of a herbal decoction from Herniaria hirsuta, a medicinal plant widely used in Morocco to treat kidney stones, by assessing the effect of oral administration in experimentally induced calcium oxalate (CaOx) nephrolithiasis in rats. MATERIAL AND METHODS: Two groups of six rats each were rendered nephrolithic by treating with ethylene glycol 0.75% and ammonium chloride 1% for 3 days, and then ethylene glycol only for 3 weeks. Maintained on ethylene glycol, one group of rats was also given 1 mL/day of the plant decoction, while the others received 1 mL of water instead for 2 weeks. Urine samples (24 h) were collected individually at 1, 3, 7, and 14 days for physicochemical analysis. On completing the treatment the kidneys were collected and analysed by light microscopy. RESULTS:
The water intake and diuresis decreased in the treated rats; there was no significant difference in urinary pH between the groups. Urinary chemistry was apparently unaffected by the plant extract, except for the magnesium content, which was higher in treated rats. Crystalluria was characterized by the excretion of large CaOx monohydrate and dihydrate crystals in untreated, but smaller crystals in treated rats. The histology showed large deposits of CaOx crystals in all parts of the kidney in untreated rats but with almost no deposits in those of treated rats. CONCLUSION: H. hirsuta has an impressive prophylactic effect on CaOx stones in nephrolithic rats; the effect did not seem to be mediated by biochemical or diuretic changes.
Atmani F, Slimani Y, Mimouni M, Aziz M, Hacht B, Ziyyat A. Effect of aqueous extract from Herniaria hirsuta L. on experimentally nephrolithiasic rats. J Ethnopharmacol. 2004 Nov;95(1):87-93. Abstract: Despite considerable progress in medical therapy, there is no satisfactory drug to treat kidney stones. Therefore, this current study is aimed to look for an alternative treatment by using Herniaria hirsuta on nephrolithiasic rats as a preventive agent against the development of kidney stones. The experiment was conducted in normal and calcium oxalate (CaOx) nephrolithiasic rats during 3 weeks. Several parameters were followed weekly including water intake, urinary volume and pH, some urinary chemistries, and crystalluria. At the end, kidneys were analyzed by light microscope. The results showed that water intake and urinary volume increased in nephrolithiasic rats, but their urinary pH decreased especially in the third week of treatment. Urinary oxalate increate significantly during the second week for untreated rats and remained constant in rats treated with Herniaria decoction. However, urinary calcium decreased significantly in week 2 in untreated rats and remained constant in treated rats. Qualitative analysis of crystalluria showed that untreated rats excreted large CaOx monohydrate and few dihydrate crystals while treated animals excreted mostly small CaOx dihydrate crystals. The examination of kidney sections revealed that CaOx deposition was limited in treated rats when compared to untreated ones.These results obtained in vivo confirmed the beneficial effect of Herniaria hirsuta and may justify its use as a preventive agent against the formation of calcium oxalate kidney stones.
Mbark AN, Charouf Z, Wray V, Nimtz M, Schöpke T. Monodesmosidic saponins from Herniaria hirsuta. Pharmazie. 2000 Sep;55(9):690-2. Abstract: Two new monodesmosidic saponins, herniaria saponins E and F, were isolated from the aerial parts of Herniaria hirsuta. On the basis of chemical and spectral evidence, their structures were established to be 2-O-acetyl medicagenic acid 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->6)]-beta-D-glucopyranoside (herniaria saponin E, 1) and medicagenic acid 28-O-beta-D-xylopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1->6)]-beta-D-glucopyranoside (herniaria saponin F, compound 2).
Rhiouani H, Lyoussi B, Settaf A, Cherrah Y, Hassar M. 2001. Antihypertensive effect of Herniaria glabra saponins in the spontaneously hypertensive rat. Ann Pharm Fr. 2001 May; 59(3): 211-4. French. Rhiouani H, Settaf A, Lyoussi B, Cherrah Y, Lacaille-Dubois MA, Hassar M. 1999. Effects of saponins from Herniaria glabra on blood pressure and renal function in spontaneously hypertensive rats. Therapie. 1999 Nov-Dec; 54(6): 735-9. A. Settaf, S. El Kabbaj, A. Labhal, Y. Cherrah, A. Slaoui, M. Hassar. Herniaria hirsuta reduces biliary cholesterol in dogs. Induced changes in bile composition.Wichtl M (ed). 1994. Herniaria herba – Rupturewort. In Herbal Drugs and Phyto-pharmaceuticals. (English translation by Norman Grainger Bisset). CRC Press, Stuttgart, pp. 263-265.