การพัฒนาสูตรตำหรับยาสมุนไพรไทยสำหรับการรักษาภาวะนิ่วทางเดินปัสสาวะ

Abstract

Urolithiasis is the third ranked prevalent disorder in the urinary system which affects health and the quality of life in world populations. Senna siamea, Gomphrena celosioides, Plantago major, Houttuynia cordata, Pseudelephantopus spicatus and Tribulus terrestris have traditionally been used to treat urolithiasis. However, there is no scientific research on these plants to determine their properties with neither as a single extract nor a formula. Thus, the objectives of this research are to evaluate the in vitro and in vivo anti-urolithiasis of these plants and to develop herbal formulas for treating urolithiasis. Each plant species was extracted with water or methanol to obtain eight extracts. These eight plant extracts were tested with four in vitro analyses; phytochemical analysis, anti-urolithiasis, anti-contraction of bladder smooth muscle, and antioxidant activities. The results of the in vitro experiment showed that all plant extracts exhibited a concentration-dependent inhibitory effect on crystal formation by reducing the number and size of calcium oxalate monohydrate crystals produced in artificial urine and these extracts effected on the morphology of calcium oxalate crystals, caused the cracks, adsorbed and coated the crystal surface to reduce an ability of aggregation and growth of crystals. The extracts could also relax the bladder smooth muscle and exhibit high antioxidant capacity. It is possible that saponins, flavonoids and phenolics found in these extracts are responsible for all tested activities. From the results of in vitro experiments, six extracts, aqueous extract of S. siamea and methanolic extracts of P. spicatus, T. terrestris, S. siamea, G. celosioides and H. cordata were selected to develop three formulas. All three formulas were then tested for acute toxicity before assessment for their anti-urolithiasis activity in the ethylene glycol-induced urolithiasis model. It was found that all three formulas showed potent anti-urolithiasis activities. Formulas 1 and 2 significantly decrease blood urea nitrogen level of the caliculi induced rats and all three formulas (50 mg./kg.) could reduce the level of urine crystals. The histopathological observations also supported the biochemical evidence of their anti-urolithiasis activities. The decrease of crystal deposition in renal tissues and the urinary bladder was clearly seen. In addition, all three formulas were able to restore the levels of superoxide dismutase, catalase and reduced glutathione in the kidneys. Moreover, the level of malondialdehyde decreased in the calculi-induced rats that were treated with formulas 1 and 2. The results from this study indicated the anti-urolithic property of all three formulas developed from Thai plant extracts. Inhibition of calcium oxalate stone formation, urinary smooth muscle relaxation and anti-oxidation are the proposed mechanisms underlying the anti-urolithic property of these formulas.