SAMBONG (BLUMEA BALSAMIFERA):
ITS EFFECT ON CALCIUM STONES *Fernando Rico, M.D.
From the Section of Urology, Department of Surgery,
ABSTRACT
The chemolytic effects of Sambong (Blumea balsamifera) in calcium stones were determined in vitro. Fresh urine sample from controls, subjects on Sambong 40 mg/ kg/ day and 60 mg/ kg/ day were used to bathe a 1 cm stone sample for 10 days. Results showed statistically significant stone dissolution of Sambong. The 40 mg/kg/day dose showed maximum therapeutic effect. The authors indicate that this drug could be a second alternative for the management of ureteral calculi especially its being a smooth muscle relaxant with diuretic effects as well.
INTRODUCTION
Sambong
(Blumea balsamifera) is a coarse, tall, erect, woody and strongly aromatic
herb. It is hairy, standing 1.5 to 3 meters long. It is ubiquitous, growing
anywhere in the
In recent years, there has been a keen revival of interest in herbal medicine, acquiring a deep significance in the country because of poor economy and rising cost of medicines. Initiated in 1997 by the Department of Science and Technology (DOST), the study of herbal plants continues to be an interesting project.
___________________
*
2nd Prize, 7th Annual PUA Resident's Research Essay Contest, 1991.
Sambong has been studied
extensively, from phytochemical to pharmacologic and toxicologic analysis.
(5) A pilot clinical study done in 1984 showed its diuretic properties
comparable to thiazides. (6) Clinical studies also showed its therapeutic
effect on hypertension and glaucoma. (7,8)
Mutagenicity studies revealed that the plant had no chromosome-breaking potential. Instead, there is a reduction in the formation of micronucleated polychromatic erythrocytes as induced by dimethylnitrosamine, tetracycline and mitomycin C, suggesting that sambong has anti-mutagenic activity. (9,10,11,12) In 1988, Fujimoto et al. concluded that sesquiterpene lactones isolated from Blumea exhibited anti-tumor activity against Toshida sarcoma cells in tissue culture.(13)
It is claimed that sambong is effective to resolve signs and symptoms of urolithiasis, cause spontaneous passage of stone and decrease the size and completely dissolve staghorn calculi. (12) Accordingly, there is value in gaining more information on Sambong as an oral chemolytic agent through clinical trials and laboratory tests.
Considering the reports and clinical studies, the spontaneous passage of stone may be due to its smooth muscle relaxant action, diuretic effect, or may happen even without Sambong treatment .(13) Diuretics like thiazides act on decreasing calcium concentration in the tubules (Jacobson and Fuchs, 1989) which is effective in treating resorptive hypercalciuria. Sigua showed the smooth muscle relaxant and diuretic action, an in vitro model is devised, simulating clinical setting, to determine its main effect on calcium stones.
The study aims to determine the effect of Sambong in calcium stones in vitro.
MATERIALS AND METHODS
Apparatus. The Flowby dissolution apparatus devised by Saltzman and Gittes15 was modified. It consists of individual intravenous fluid bottles as reservoir for the urine infusion and an output intravenous tubing (venoset, macrodrip). The tubing was connected to the tip of the plunger of a 30 cc syringe so that its tip penetrated the rubber tip. The syringe which housed the one cm calcium stone had an outlet connected to another tubing connected to a drainage bottle. The syringe with the stone was immersed in a shaking warm water bath regulated at 37 °C to simulate clinical setting. Urine infusion rates were hand regulated with the use of venoset control. (Figure 1)
Figure 1. Modified Flowby Dissolution Apparatus
Stones: Calcium stones had been retrieved by open operation from a patient with multiple stones. Stones were analyzed using Merckognost urinary stone analysis kit.
Chosen size of stone for analysis was one cm. Fragments from larger stones were also rounded at one centimeter diameter. The stone was air dried until a constant weight was obtained on the front loading mettler balance. The stones for each comparative trial were of approximate size and weight and taken from adjacent location, if fragments were from a larger stone.
Solution.
Urine was used as clysing media taken from 15 normal subjects. There were
8 males and 7 females with an average age of 22.86 ( range : 12 - 42 years).
Inclusion criteria for normal were :
Ø good renal function using serum creatinine
Ø normal urinalysis and
Ø no recent intake of other medicines
Procedure: A total of 45 trials were done on 15 subjects with double cross
over analysis. Fresh urine samples were simultaneously collected from 15 subjects
equally grouped into :
A. Five control subjects did not take Sambong
B. Five subjects took Sambong (40 mg/kg/day); this is the recommended dose
of Sigua, et al. in the treatment of urolithiasis.
C. Five subjects took Sambong (60 mg/kg/day).
Sambong was prepared in tablet form (250 mg/tablet) by UP-PGH Pharmacology Laboratory. Each trial lasted for ten days which started after one day regular oral intake of Sambong to achieve maximal urinary concentration. Two cross-over studies were done to obviate internal differences among the group and also, obtain a total of 45 trials. After 1 week rest of medication to fully excrete all prior intake of Sambong and to air dry the same stone samples, a cross-over was done. (Figure 2).
All 15 subjects were monitored for oral fluid intake (maintenance: 2.5 - 3.5 liters/day) and urine output. Stones were taken from a single patient with staghorn calculi (extracted during bivalve operation) to preclude quality (of stone) as a variable in the study. Result of stone analysis is shown in Figure 3. One centimeter was chosen because this is the average size applicable in the medical management of patients with pelvoureterolithiasis. Smaller sized stones may spontaneously pass out without surgical intervention(16). The stones studied were of approximately the same size and weight. Some were broken from the larger pelvic stone and were analyzed simultaneously on a trial.
Stones were weighed on a Mettler balance scale to get the constant weight after air-drying and before the start of each trial. The stones were taken out after ten days from the syringe and again, air-dried to get the constant weight for the next cross-over trial. Stones were placed in a 30 cc syringe with the tip of the plunger at the 10 cc mark, simulating the normal volume capacity of the pelvis.
All syringes containing the stone were immersed in a shaking warm water bath ( LKB multi-temp model 22°9) at 37°C.
Ten day continuous clysis of fresh urine was regulated at 40 cc/hr approximately 11/day which is the average urine production per kidney.
Ten to twenty cc urine samples were taken on all trials pre- and post- clysis and were analyzed for their quantitative calcium content using atomic absorption spectrophotometry (1L 257). The amount of calcium in parts per million(ppm) unit that was dissolved into urine solution was calculated subtracting pre-clysis with post-clysis calcium concentration. The results of the 3 groups were then plotted on a linear curve graph, compared, and analyzed.
RESULTS
The over-all effect of Sambong on stone dissolution was analyzed using a step-wise
regression analysis. Result showed that all the dosage including the control
(dose = 0 mg/kg BW/day) had statistically significant dissolution ( p=<
0.001). On the other hand, comparing the regression of the lines and rate
of dissolution of calcium per unit increase in time of the 3 dosages revealed
that the 40 mg dose had a far better result than the rest. (Figure 4). The constant regression coefficient
and dissolution rate values are shown in Figure 4.
Separate comparison of regression lines of 3 dosages at 3 cross-over periods was made and showed not much difference with highly significant p value (<0.001) except on the first cross-over at 0 mg dose. (Figure 5). Comparison of calcium dissolution to dosage and period of irrigation (10 Days) using 2-way analysis of variance, all showed significant p values (<0.001) except on the dosage variance on the first day of irrigation (p greater than or equal to 0.05).(Figure 6)
To determine whether the cross-over and grouping had any influence, all were subjected to 2-way analysis of variance. Result revealed that both had no statistically significant effect on the study. Group p value = 0.8524 (> 0.05) and cross-over p value = 0.4740 ( > 0.05). (Figure 7.)
The total amount of calcium concentration (ppm unit) per subject was correlated with the amount of weight reduction of stone samples on all cross-over trials. Correlation values were: cross-over I = 0.862, cross-over II = 0.673 and cross-over III = 0.086. This explains that the trend is a decreasing correlation, which is far from a perfect 1:1 ratio. The total weight reduction appears to be a bit less than calcium concentration computed from the solution. Poor correlation was noted on the last cross-over which maybe due to some increase in weight in 40 mg dose despite irrigation.
The mean, standard deviation, skewness, kurtosis, minimum and maximum values of dissolved calcium were evaluated and compared on all three dosages. This shows that the 40 mg dose had the greatest mean = 86.17, large SD = 20.79, and the widest range of calcium dissolution. Result of 0 and 60 mg are also shown in Figure 8. This means that there is a wider and higher range of dissolution in the 40 mg dosage. Dissolution will go faster in one person than with another on the same dosage.
DISCUSSION
Medical management of urolithiasis was initiated in 1873 when Sir Henry Thompson thought of the possibility of treating bladder stone by dissolution.(17) Galen even treated stone disease with wine and honey, parsley and caraway seed. Howship and Sir Astley Cooper used alkalis and acids to arrest growth of calculi. (18)
The advent of high technology in the management of urolithiasis ( i.e. laser endoscopic lithotripsy and ESWL) notwithstanding, stone chemolysis ( oral systemic or direct irrigation through a nephrostomy tube or ureteral catheter) plays a major role in stone therapy.
Stone fragments are commonly left behind during an operation for renal struvite calculi. While Boyce and Elkins observed retained fragments in only five percent, others reported an incidence of up to forty percent . Residual fragments are small and can only be identified by nephrotomography; indeed, silent calculi have been observed in 26 - 40 percent of the patients when intra-operative nephroscopy and coagulum pyelolithotomy have been used in management. Micro-particles of stone are not uncommonly left post-operatively.(19) other techniques to enhance complete stone removal are: anatrophic nephrolithotomy, extended pyelolithotomy, regional renal hypothermia, intra-operative radiography and post-operative renal irrigation with different solutions ( including the local study on bukolysis by Macalalag).(20)
The advantages of sambong in the treatment of urolithiasis are as follows:
1.
Avoiding surgery , especially on poor surgical risk patients;
2. Post-operative adjuvant treatment for residual calculi or stone fragments
which could be a nidus for re-growth f calcium stones;
3. Alternative regimen in the primary medical management of urolithiasis,
especially on small ureteral stones, being a smooth muscle relaxant, diuretic
and a chemolytic agent, as well; and
4. Cost benefit.
This study as conceptualized from the experience of Sigua in stone treatment
using Sambong as follows:
1.
Stone composition not known,
2. Size and number of stones vary, and
3. Controversy as to how stones pass after sambong treatment.
In this study, only one stone of uniform size and quality was used so that stone fragility, density and surface area were not considered as variables. Moreover, Sambong's smooth muscle relaxant and diuretic effects were precluded.
Almost all the results were statistically significant providing that Sambong really has a chemolytic effect which is maximal at 40 mg/kg BW/day dose. It is therefore resumed that it is its maximum therapeutic dose in this study. Stepwise regression analysis also showed that 40 mg has the greatest calcium dissolution per unit increase in time. Analysis of variance showed that the cross-over and grouping had no influence on the result.
However, there appears to be a poor correlation between weight reduction of stone samples and calcium concentration (post-clysis minus pre-clysis) presumed to be taken from stone samples. This may be due to inaccuracy of dry weighing of stone.
The problem presented in this study is the limited time (10 days) in which continuous clysis with daily analysis was done. This does not give an ideal predictable time of dissolution or evaluate dissolution rate.
This preliminary study shows that sambong is a promising chemolytic agent for calcium stones and needs further clinical trial as to highly recommend its commercial use for stone treatment. Moreover, this study also recommends the analysis of the active component of Sambong's chemolytic property to obtain optimum concentration for dissolution.
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