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Phyllanthus niruri as a Promising Alternative Treatment for Nephrolithiasis

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In spite of considerable efforts to identify effective treatments for urolithiasis, this is a goal yet to be achieved. This review summarizes experimental and clinical data evaluating the effect of the plant Phyllanthus niruri, a plant with worldwide distribution, as a potential agent to prevent and/or to treat urolithiasis The review is based on data from the literature and on the results obtained by our group from either in vivo/in vitro experiments or clinical studies. Phyllanthus niruri has been shown to interfere with many stages of stone formation, reducing crystals aggregation, modifying their structure and composition as well as altering the interaction of the crystals with tubular cells leading to reduced subsequent endocytosis. The clinical beneficial effects of Phyllanthus niruri may be related to ureteral relaxation, helping to eliminate calculi or to clear fragments following lithotripsy, or also to a putative reduction of the excretion of urinary crystallization promoters such as calcium. No adverse renal, cardiovascular, neurological or toxic effects have been detected in either of these studies. Altogether, these studies suggest a preventive effect of Phyllanthus niruri in stone formation or elimination, but still longer-term randomized clinical trials are necessary to confirm its therapeutic properties.
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Phyllanthus niruri as Treatment for Nephrolithiasis
International Braz J Urol Vol. 36 (6): 657-664, November - December, 2010
Phyllanthus niruri as a Promising Alternative Treatment for
Nephrolithiasis
Mirian A. Boim, Ita P. Heilberg, Nestor Schor
Renal Division, Federal University of Sao Paulo, Unifesp, Sao Paulo, Brazil
ABSTRACT
In spite of considerable efforts to identify effective treatments for urolithiasis, this is a goal yet to be achieved. This review
summarizes experimental and clinical data evaluating the effect of the plant Phyllanthus niruri, a plant with worldwide
distribution, as a potential agent to prevent and/or to treat urolithiasis The review is based on data from the literature and
on the results obtained by our group from either in vivo/in vitro experiments or clinical studies. Phyllanthus niruri has
been shown to interfere with many stages of stone formation, reducing crystals aggregation, modifying their structure and
composition as well as altering the interaction of the crystals with tubular cells leading to reduced subsequent endocytosis.
The clinical beneficial effects of Phyllanthus niruri may be related to ureteral relaxation, helping to eliminate calculi or to
clear fragments following lithotripsy, or also to a putative reduction of the excretion of urinary crystallization promoters
such as calcium. No adverse renal, cardiovascular, neurological or toxic effects have been detected in either of these stud-
ies. Altogether, these studies suggest a preventive effect of Phyllanthus niruri in stone formation or elimination, but still
longer-term randomized clinical trials are necessary to confirm its therapeutic properties.
Key words: renal; lithiasis; treatment; clinical; Phyllanthus niruri
Int Braz J Urol. 2010; 36: 657-64
INTRODUCTION
Urinary stones affect 10-12% of the popula-
tion in industrialized countries. Their incidence has
been increasing over the last years and the age of
onset is decreasing. In addition, the recurrence rate
is high, more than 50% after 10 years (1,2). Genetic,
metabolic, environmental and dietetic factors are
involved in the pathogenesis of urolithiasis, all of
them propitiating the crystallization of salts inside the
renal tubules, further retention and growing to form
a stone (3). Given that urine is normally a supersatu-
rated solution, crystalluria is often observed in normal
individuals, but if crystals remain apart from each
Review ArticleReview Article
doi: 10.1590/S1677-55382010000600002
other, they are washed away by urine flow. However,
under certain circumstances they bind each other due
to chemical and electrical forces triggering the process
of aggregation. The crystals or aggregates then attach
to the epithelium which allow them to grow further
and form the stone (4). Moreover, calcium oxalate
(CaOx) crystals, the main constituent of human uri-
nary calculi, may adhere in a specific manner to the
plasma membrane of epithelial cells and this process
is followed by endocytosis of the crystals resulting
in cell damage or death (5,6). Damaged cells exhibit
a proliferative response, increase the synthesis of
fibrogenic substances promoting additional stimulus
for crystal growth (7,8). In addition, dead cells detach
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Phyllanthus niruri as Treatment for Nephrolithiasis
from the basement membrane and the cellular debris
will adhere to other crystals resulting in a stone nidus.
Thus, the cellular pathways involved in endocytosis of
CaOx crystals can constitute potential targets for drugs
designed for the prophylaxis and/or treatment of uro-
lithiasis. Different substances have been described as
modulators of adhesion and/or endocytosis processes
(9-11) but none of them seem to be suitable for clinical
use. On the other hand, alternative treatments such
as the traditional herbal treatments can compliment
pharmacotherapies for prevention and/or treatment of
urolithiasis with less expense and perhaps fewer side
effects, as reviewed by Miyaoka and Monga (12).
We have been evaluating the effects Phyl-
lanthus niruri on several stages of stone formation as
well as its potential therapeutic potential in lithiasic
patients. Experimental and clinical studies performed
by our group and by others have produced interesting
and hopeful data concerning the potential therapeutic
use of Phyllanthus niruri to treat and/or to prevent
stone formation. These data are summarized in this
review.
PHYLLANTHUS NIRURI
Phyllanthus niruri, popularly known as
“stone-breaker” (“quebra-pedras”) is a plant belong-
ing to the Euphorbiaceae family with a worldwide
distribution and it is used in folk Brazilian medicine
for patients with urolithiasis (13). More than 50
compounds were identified in the Phyllanthus niruri,
including alkaloids, flavanoids, lignans and triterpenes
(14). Among these substances, the triterpenes have
been found to inhibit the cytotoxicity induced by
calcium oxalate (15) as well as to reduce excretion
of stone forming constituents (16) and the markers
of crystal deposition in the kidneys (17). Moreover,
methanol extract from the leaves of Phyllanthus niruri
containing substances such as lignans and phyllanthin
showed a uricosuric activity in hyperuricemic rats
(18). According to Calixto et al. (19) alkaloids ex-
tracted from plants of the genus Phyllanthus present
an antispasmodic activity leading to smooth muscle
relaxation, mostly evidenced in the urinary tract,
which would facilitate the elimination of urinary
calculi. These data strongly suggest that Phyllanthus
niruri may be a potential source of many substances
with antilithiasic properties.
Interestingly, given that the maintenance of
normal levels of calcium is critical to the function
of many plants including plant rigidity, protection,
detoxification (heavy metals or oxalic acid), ion bal-
ance and even light reflection (20), and because high
cellular free calcium concentration may be dangerous
for these organisms, higher plants (plants exhibiting
a vascular system) developed a very efficient way
to neutralize Ca+2 ions, by forming complexes with
oxalate (21). Oxalate producing plants, which include
many crop plants, accumulate oxalate and as much as
90% of the total calcium in the form of CaOx crystals.
Curiously, as shown in Figure-1, refractive CaOx
crystals seen in the leaves of Phyllanthus niruri are
kept equidistant, do not aggregate hence not forming
stones. Therefore, understanding the basic molecular
strategies by which some plants are able to package
CaOx crystals may provide insights into the potential
utilization of these plants to prevent/treat urolithiasis
(22).
IN VITRO STUDIES
The effect of the aqueous extract of Phyl-
lanthus niruri on crystallization process of CaOx in
human urine has also been investigated in a model of
in vitro precipitation of CaOx in human urine (23).
Barros et al. (24) observed that the pre-incubation of
Figure 1 – CaOx crystals observed in Phyllanthus niruri leaves
observed under light microscopy.
659
Phyllanthus niruri as Treatment for Nephrolithiasis
human urine with Phyllanthus niruri did not inhibit
the precipitation of CaOx particles and even more
crystals were obtained in Phyllanthus niruri-contain-
ing urine, but the crystals were proportionally smaller
than those in urine samples without Phyllanthus
niruri. Moreover, they observed that after 24 hours,
the precipitated crystals formed large agglomerates in
untreated urine, but the crystals remained dispersed in
urine with Phyllanthus niruri (Figure-2). The authors
concluded that Phyllanthus niruri did not decrease the
number of crystals but induced a marked reduction of
particle size and crystal aggregation. Similar results
were obtained by Atmani E and Khan SR (25) employ-
ing a different plant species (Herniaria hirsute), which
is used in folk medicine in the Mediterranean area for
its diuretic properties and to treat kidney stones. Crys-
talluria is a common event observed even in non-stone
forming individuals. CaOx crystals are found in urine
under several forms including monohydrate (COM)
and dihydrate (COD) forms. Unlike COD, which is
predominantly found in normal individuals, COM
crystals have higher capacity to aggregate and adhere,
and is the main form excreted by the nephrolithiasis
patients (26-28). In the model of in vitro precipitation
of CaOx using human urine from healthy individuals,
Phyllanthus niruri induced an increase in COD forms
and reduced the amount of COM crystals, responsible
for higher potential risk for stone formation.
Besides CaOx crystallization, it has been
shown that the methanol extracts of Phyllanthus
niruri showed an inhibitory activity of the enzyme
xanthine oxidase in vitro (29) which was attributed
to compounds such as flavonoids, polyphenols and
tannins (30,31). Therefore, together with its uricosuric
property (18), this enzymatic inhibition activity makes
Phyllanthus niruri a potential antihyperuricemic
agent.
STUDIES IN CULTURED CELLS
Campos and Schor (32) have demonstrated
that Phyllanthus niruri exhibited a potent inhibitory
effect on CaOx crystal adhesion and/or endocytosis
Figure 2 – Light microscopy of CaOx crystals formed immediately (0 hr) and 24 hours after the addition of sodium oxalate solution in
normal human urine and after in the absence and presence of Phyllanthus niruri. X100 and X400.
660
Phyllanthus niruri as Treatment for Nephrolithiasis
by an immortalized cell line derived from canine
kidney (MDCK cells) representative of the medullar
collecting duct. This type of inhibitory effect occurred
even when high doses (2.5 to 5-fold the upper limit
in human urine) of CaOx have been employed and
without causing cell toxicity.
EXPERIMENTAL MODELS IN RATS
The effect of Phyllanthus niruri has also been
evaluated in experimental models of urolithiasis in
rats, mainly those induced by implantation of a cal-
cium oxalate (CaOx) crystal into the bladder (vesical
foreign body method). This experimental model of
urolithiasis is obtained with no significant metabolic
or systemic alterations and the vesical CaOx seed acts
as a supporting surface allowing organic and inorganic
material to precipitate over the central nidus, mimick-
ing a spontaneous calculus growth. It was initially
shown that rats drinking Phyllanthus niruri tea ad
libitum, presented decreased rate of stone growth (33).
These effects occurred independently of any relevant
modification in the urinary excretion of elements
known to promote crystallization and stone formation,
including calcium, oxalate, uric acid, pH, etc. In order
to evaluate if the beneficial effect of Phyllanthus niruri
could be mediated by modifications of the inhibitors
of stone formation, such as citrate, magnesium and/or
glycosaminoglycans, Freitas et al. (34) administered
1.25 mg/mL/day of Phyllanthus niruri for 42 days in
rats with vesical CaOx seed. This chronic treatment
induced a significant reduction in the calculi growth,
in the absence of any modification in the volume
diuresis or alterations in the urinary concentration of
lithogenic elements including calcium and oxalate.
Phyllanthus niruri administration did not modify the
urinary excretion of citrate and magnesium, indicating
that the putative antilithogenic effect of Phyllanthus
niruri was not primarily mediated by modifications
in these inhibitors. In contrast, it was observed that
Phyllanthus niruri induced a decrease in the urinary
excretion of glycosaminoglycans (GAGs) compared
with lithiasic animals receiving water. In contrast, the
content of GAGs was higher in calculi taken from
treated animals suggesting that the inhibitory effect
Phyllanthus niruri on crystal growth might have been
related to higher incorporation of GAGs into the
calculi. The adsorption of these macromolecules into
the calculi lead to stones with a predominant intrac-
rystalline amorphous organic matrix. Taken together,
these results suggested that Phyllanthus niruri was
able to prevent the aggregation of calcium oxalate to
the pre-existent crystal without interfering with the
incorporation of GAGs into organic matrix. Although
the underlying mechanism remains to be clarified,
some possible hypotheses can be raised: 1) a neu-
tralization of negative charges of GAGs reduced the
negative pole for progressive deposition of cations; 2)
active components of the plant could have chelated
and/or competed with calcium for binding sites on the
crystal surface; 3) effects of Phyllanthus niruri itself
on other proteins including Tamm-Horsfall protein,
nephrocalcin, osteopontin, prothrombin fragment 1,
etc, modulating crystallization, aggregation and cal-
culi growth and 4) Phyllanthus niruri could reduce the
crystal adhesion to the tubular epithelium. Essentially,
these results suggest that Phyllanthus niruri could
interfere with the calculi growth or prevent stone
formation rather than dissolving pre-formed stones.
In order to better mimic what is observed
in clinical practice, Barros et al. (35) using a vesical
foreign body model in rats, compared the efficacy of
Phyllanthus niruri treatment started concomitantly
with CaOx seed implantation with the same treatment
started 30 days after the seed implantation (when the
vesical calculus was completely formed). As repre-
sented in Figure-3, the early treatment (Figure-3A)
caused a significant inhibition in the calculi growth
compared with non-treated animals (Figure-3B), as
previously observed (34). In contrast, the treatment
initiated after the stone formation, did not prevent
the calculi to grow further neither propitiated calculi
elimination; however it induced drastic changes in
the shape and texture of the preformed calculi (Fig-
ure-3C). Stones taken from Phyllanthus niruri treated
animals were more homogeneous and contained more
compact surfaces (Figures 3D and 3E) in contrast
to the spicule-shaped surface taken from untreated
animals (Figure-3F). This result suggests that Phyl-
lanthus niruri probably interferes with the biominer-
alization process, by promoting a different interaction
between the crystal and the macromolecules of the
organic matrix. Although Phyllanthus niruri had not
661
Phyllanthus niruri as Treatment for Nephrolithiasis
Figure 3 – Upper and lower panels show the stereomicroscopy and scanning electronic microscopy respectively of the calculi taken
from animals untreated (A and D), animals treated from the beginning (B and E) and from later treated animals (C and F).
A B C
D EF
prevented the calculi growth, the treatment resulted
in the formation of calculi with smoother surfaces,
which could at least, contribute to less painful calculi
voiding.
CLINICAL STUDIES
The initial study (33) addressing the effects
of the Phyllanthus niruri administered in the form
of tea did not demonstrate any clinical or biochemi-
cal adverse effects (cardiovascular, renal, hepatic or
neurological) even at high dosage, with excellent
tolerability in healthy volunteers. In addition, tea con-
sumption in the same dose by nephrolithiasis patients
for a period of 3 months, led to an apparent increased
elimination of calculi compared to patients drinking
placebo. These results were probably ascribed to the
antispasmodic and relaxant effects of Phyllanthus
niruri upon ureteral muscle, facilitating calculi void-
ing.
Subsequently, another study by Nishiura et
al. (36), also in our Service, evaluated the effect of a
lyophilized 2% aqueous extract of Phyllanthus niruri,
in an additional series of 69 lithiasic patients in the
form of 450 mg capsules (three times a day) compared
with placebo (Chicorium sativum). In this short-term
follow-up conducted during a three-months period,
no significant differences in calculi voiding and/or
pain relief between the groups taking Phyllanthus
niruri or the placebo were detected. However, as
patients were classified according to the presence of
metabolic disturbance, a significant reduction in the
mean urinary calcium excretion was observed only
among hypercalciuric patients. The phytochemical
and pharmacological properties of this plant have
been accounted for the action of different substances
such as Rutin, beta-amylin, beta-sitosterol, caffeic
acid, geranin, quercetin, niruside and repandusinic
acid. Although none of these compounds has been
shown to have an effect on calciuria to date, such
potential beneficial effect of Phyllanthus niruri for
hypercalciuric patients needs to be further confirmed
in longer-term studies involving a higher number of
subjects.
Micali and coworkers (37) observed that
patients submitted to extracorporeal shock wave
lithotripsy and treated with Phyllanthus niruri during
662
Phyllanthus niruri as Treatment for Nephrolithiasis
3 months presented lower incidence of residual stone
fragments, mainly those in lower calyceal location
compared with non-treated patients. According to
these investigators, the efficacy and the lack of side
effects of Phyllanthus help improve overall outcomes
after extracorporeal shock wave lithotripsy and could
be useful as either an alternative or an adjunctive
therapy in the treatment of urolithiasis.
Table-1 summarizes the main findings in
all studies. Given the experimental characteristic of
these studies, except for the clinical ones (Grade of
recommendation B), an exact level of evidence is not
applicable.
CONCLUSION AND PERSPECTIVES
The experimental studies summarized here
suggest that Phyllanthus niruri might interfere with
important steps of the calculi formation including
crystal aggregation and internalization by the tubular
cells, crystal structure and composition. These proper-
ties of Phyllanthus niruri may constitute an important
advantage in the prevention of lithiasis, inhibiting
calculus growth and keeping the crystals dispersed
in the urine, with their consequent easier elimination.
Although clinical studies are less abundant, available
data point to beneficial effects of Phyllanthus by in-
ducing ureteral relaxation, interfering in the excretion
Table 1 – Summary of main findings.
Studies Main Findings Reference
Models in vitro Inhibition of CaOx crystal adhesion and/or endocytosis
Reduction in crystals aggregation
Increase in COD forms and reduced COM crystals
32
24
24
Models in vivo Decreased rate of stone growth
Increase intracrystalline amorphous organic matrix
Changes in the shape and texture of the preformed calculi
34,35
34
35
Clinical Increased calculi voiding
Reduction in urinary calcium excretion in hypercalciuric patients
Reduction in residual stone fragments after extracorporeal shock
wave lithotripsy
33
36
37
COM = calcium oxalate monohydrate; COD = calcium oxalate dihydrate.
of promoters of urinary crystallization such as calcium
or helping to clear fragments following lithotripsy. It
is important to consider however, that although it is
clear that Phyllanthus niruri can interfere with many
steps of the stone formation, longer-term clinical stud-
ies are necessary to define whether these effects can
be translated into real clinical benefit to treat and/or
prevent urolithiasis.
CONFLICT OF INTEREST
None declared.
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Accepted after revision:
May 26, 2010
Correspondence address:
Dr. Mirian A. Boim
Renal Division, UNIFESP
Rua Botucatu, 740
04023-900, São Paulo, SP, Brazil
Fax: + 55 11 5904-1684
E-mail: mirian@nefro.epm.br
EDITORIAL COMMENT
The authors provide a nice review on the herb
Phyllanthus niruri whose properties appear in fact to
be promising assets in stone disease prevention and
treatment. However, care must be taken to properly
design future clinical studies in a way to provide re-
liable, consistent and reproducible data. As a major
concern, I would point out the definition of accurate
dosage and mode of intake. In a recent review on Chi-
nese herbs used for managing stone disease, Miyaoka
et al. (1) found several clinical trials demonstrating the
likely benefits on stone prevention. However, the lack
of standardization on dose and compounds between
studies evaluating the same herbs made it extremely
difficult to compare them and draw a sustainable
conclusion. As a result, although used for hundreds
of years with practical evidence of clinical benefits,
Chinese herbs still strive to enter the armamentarium
of stone therapy as a global consensus.
REFERENCE
1. Miyaoka R, Monga M: Use of traditional Chinese
medicine in the management of urinary stone disease.
Int Braz J Urol. 2009; 35: 396-405.
Dr. Ricardo Miyaoka
Division of Urology
University of Campinas, UNICAMP
Campinas, SP, Brazil
E-mail: rmiyaoka@uol.com.br
... This plant is commonly known by the Brazilians as Chanca piedra Piedrawhich also translates to "stone breaker" [4]. The plant was reportedalso has the capability to reduce pain, urinary calcium in patients with hypercalciuria, expel intestinal gas, stimulate and promote digestion, expel worms as a mild laxative, the aqueous extract was also known to inhibit HIV-1-reverse transcriptase [5,6].Chanca piedra (Phyllanthus niruri) is used for so many purposes in the herbal medicine system. It is also employed for hypertension due to the existence of geranin, and high cholesterol levels control. ...
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The toxicity effect of Chanca piedra (Phyllanthus niruri)leaves extract was studied on albino rats. Rats were divided into four groups, four per group. Group 1 received water and feeds only, whileonly. Groups 2, 3, and 4 were administered doses of the extract 200 mg/kg, 400 mg/kg, and 800 mg/kg body weight respectively. Parameters studied were indices of liver and kidney function. Results showed that final body weight, serum, AST, ALP, urea, Creatinine, and some electrolytes were not affected by the administration of the different doses of the extract. ALT significantly increased by administration of 200 mg/kg and 400 mg/kg of the extract when compared with the control. Besides, there was asignificant increase in the level of K+ (P>0.05) at the dose of 200mg/kg body weight of the extract. Similarly, Na+ was also significantly increased by the administration of the extract (400 mg/kg and 800 mg/kg). These increases observed may be due to the certain phytochemicals present in the extract. The longer administration of the extract could likely not to be safe.
... Seeds with many discrete points, about 1 mm big. In its composition, the presence of flavonoids, lignins, salicylic acid, alkaloids, and phenolic compounds is mentioned (Pastorini 2010;Boim et al. 2010;Soares 1997). Species native to America can be found in all regions of Brazil, in addition to China, India, and in all tropical and subtropical countries (Kaur et al. 2017;Rocha et al. 2018;Santos et al. 2018). ...
... A 1 mg/mL solution of CaOx crystals was prepared in Tris-HCl (0.05 mol/L) and NaCl (0.15 mol/L) buffer at pH 6.5. About 100 µL of CF (2,4,6,8, and 10 mg/mL) was added to the buffered solution of CaOx crystals and was mixed properly and the absorbance read at 620 nm wavelength. Experiment with each test sample was carried out in triplicates [36,37]. ...
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Pleurolobus gangeticus (L.) J. St.- Hil. ex H. Ohashi & K. Ohashi (Fabaceae) is an important medicinal plant used to treat various ailments. In this study, we report the antiurolithiatic, antioxidant, and antibacterial potential of chloroform fraction (CF) from P. gangeticus roots. For the chemical profiling, HPTLC, FT-IR, and GC–MS techniques of the CF were carried out, and phytochemical investigation was revealed that stigmasterol (45.06%) is one of the major components present in the fraction. The nucleation and aggregation assays were used to evaluate the in vitro antiurolithiatic activity at various concentration (2–10 mg/mL) of the CF. The results showed that the chloroform fraction had dose-dependent effects on Calcium Oxalate (CaOx) crystal formation. In both the assays, the maximum concentration of 10 mg/mL has shown better results. This concentration resulted significant increase in CaOx crystal nucleation along with the reduction of crystal size and the inhibition of crystal aggregation. Further, the CF showed stronger antioxidant (DPPH, NO, SOD, TRC) potential with an IC50 values of 415.9327, 391.729, 275.971, and 419.14 µg/mL, respectively. The antibacterial evaluation displayed effective results in the Agar well diffusion assay against selective urinary tract infection (UTI) pathogens (Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus). A maximum zone of inhibition (ZOI) 12.33 ± 1.05 mm for K pneumonia and minimum ZOI of 8.46 ± 0.27 mm for S. aureus were obtained. Further, the ADME-PK property of the stigmasterol was investigated, and it was found to pass the Lipinski and Ghose rules, supporting the drug-likeliness. This is the first record of the antiurolithiatic potential of P. gangeticus along with antioxidant and antibacterial activities. These findings give an insight into the effective drug development and treatment for kidney stones in future.
... [110] P. niruri, popularly known as 'quebra-pedra' or 'stone-breaker' in English, is a plant used in homemade remedies in folk medicine as a protective agent for liver diseases and to eliminate kidney stones in patients with nephrolithiasis. [154][155][156] Reviews of preclinical and clinical evidence suggest that extracts and isolated compounds from P. niruri have potential hepatoprotective activity, although the heterogeneity of study protocols and lack of mechanisms of action require further investigations. [156,157] It is noteworthy that an early study performed by Venkateswaran et al. [98] investigated the activity of an aqueous extract of P. niruri on HBV-like virus replication using a woodchuck hepatitis model, demonstrating inhibition of virus replication and a lack of liver pathological effects after its intraperitoneal injection for 10 weeks. ...
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... Brazilian Journal of Animal and Environmental Research, Curitiba, v.5, n.2, p. 1532-1543, abr./jun., 2022 Diagnóstico y Seguimiento. -Se realizaron análisis de laboratorio a los pacientes (Ultrasonido de vejiga (UV) y examen general de orina (EGO) del mismo modo; terminado el tratamiento se les practico exámenes confirmatorios al tratamiento con hojas de níspero (BARTGES & CALLENS, 2015;BOIM et al., 2010;BERISTAIN-RUIZ et al., 2009;BEAUFAYS et al., 1995). ...
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... Brazilian Journal of Animal and Environmental Research, Curitiba, v.5, n.2, p. 1532-1543, abr./jun., 2022 Diagnóstico y Seguimiento. -Se realizaron análisis de laboratorio a los pacientes (Ultrasonido de vejiga (UV) y examen general de orina (EGO) del mismo modo; terminado el tratamiento se les practico exámenes confirmatorios al tratamiento con hojas de níspero (BARTGES & CALLENS, 2015;BOIM et al., 2010;BERISTAIN-RUIZ et al., 2009;BEAUFAYS et al., 1995). ...
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... It is cited in RENISUS (MS, 2010), and its use is recommended in both the RDC 10/2010 (Anvisa, 2010) and the Herbal Medicine Compendium (Anvisa, 2011;2021). Preclinical and clinical studies have demonstrated its anti-urolithic activity (Boim, et al., 2010) as well as other pharmacological ...
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Medicinal plants continue to be appropriate and preferred alternatives for primary health care among rural Amazon populations, although their incorporation into conventional health services has been slow and challenging. Besides that, few Amazon plants have been considered in current public health policies. We sought here to better understand the role of medicinal plants in the therapeutic practices of residents of the Paulo Fonteles Land Settlement at Mosqueiro, a district within Belém (Pará State, Brazil) and identify species of potential value for government health services. Ethnobotanical data was obtained through semi-structured interviews with 61 residents. Results were analyzed using indices of use-report (Ur) and by consulting official documents of the Brazilian Ministry of Health (MS). The settlers use at least 61 exotic plants and 67 natives to Brazil; of the latter species, 21 were endemic to the Amazon region. The medicinal plants cited by the settlers were used for treating 76 symptoms and/or illnesses, especially related to digestive, respiratory, dermatological, and women's health problems; Anacardium occidentale, Alternanthera brasiliana, and Dalbergia monetaria had the highest URs. Forty plants are cited in MS documents. This research incentive more studies with Amazonian species and shows a list of 11 species for inclusion in health services offered to local populations.
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Kidney stones are among the oldest and most widespread urinary tract ailments, impacting people all over the globe with a high recurrence rate. The mechanism of kidney stone formation includes events such as urine supersaturation, aggregation, retention, nucleation, and growth of crystals in the cells of the renal tubular epithelium. Kidney stones may cause extreme pain and blockage of urine flow. They are usually treated with synthetic drugs and extracorporeal shock wave lithotripsy (ESWL) as well as a variety of medications that may cause several adverse effects. The remaining stone fragments and the risk of infection following ESWL are severe problems in the treatment of kidney stones. Recently, despite the emergence of synthetic drugs, medicinal plants have been recognized and utilized in many nations due to their safety profile, efficiency, cultural acceptance, and fewer side effects than synthetic drugs. Medicinal plants are used in different cultures as a reliable source of natural remedies. The aim of this review is to provide comprehensive information about traditionally used antiurolithiatic plants as well as their scientifically proven pharmacological activities, their primary chemical ingredients, and potential mechanisms of action, such as analgesic, astringent, demulcent, diuretic activity, antioxidant activity, inhibition of the inflammatory process, nucleation inhibition, crystallization inhibition, inhibition of crystal aggregation, reducing hyperoxaluria, reducing stone size, and reducing urine supersaturation.
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Extraction of Phylllantus amarus plant powder using hot percolation and cold percolation techniques revealed the presence of alkaloids, flavonoids, terpenoids, volatile oil, saponin, tannin, anthraquinone, cardiac glycosides, phenolic compounds, reducing and non-reducing sugars. The hot percolation crude extract also revealed higher scavenging activity compared with ascorbic acid (standard reference) and cold percolation crude extract. Pre-incubation of human urine with hot percolation and cold percolation crude extract of Phyllanthus amarus to determine its effect on crystallization process of crystal salts (calcium oxalate, calcium phosphate and cysteine) which causes nephrolithiasis (kidney stone) yielded excellent results on calcium phosphate (100% effective), calcium oxalate (97% and 85.67%) while cysteine (91% and 84.67%). A total of fifteen (15) flavonoid compounds identified in the hot and cold percolation extract of Phyllanthus amarus using gas chromatography analysis include flavan-3-ols, flavones, flavonols, flavanones and isoflavanones. High flavonoid content in the hot percolation crude extract was due to the presence of significant concentrations (mg/100ml) of quercetin (282.50), catechin (16.32), kaemferol (214.33), luteolin (51.79), apigenin (1.33), epicatechin (4.13), isorhamnetin (5.49), and rutin (11.72). The sensitivity pattern of Phyllanthus amarus leaf extract towards test organisms (Pseudomonas aeruginosa, Escherichia coli Proteus mirabilis and Klebsiella pneumonia) were determined using agar well diffusion technique. All test organisms were extremely sensitive to hot percolation extract of Phyllanthus amarus compared to cold percolation extract and antibiotics used as standard reference. Prevention of renal stone and urinary tract infection recurrence is a serious problem in human health but results obtained in this research shows that Phyllanthus amarus leaf is a good source of effective crude inhibitors for crystal formation which can be used in the treatment of kidney stone, urinary tract infection and other reactive oxygen species (ROS)-related disorders.
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To assess the evidence-based literature supporting the use of traditional Chinese medicine Kampo herbal and Acupuncture in stone disease management. Four of the most commonly used herbal components of Kampo medicine in the treatment of stone disease are described according to their in vitro and in vivo effects. We also reviewed the role of Acupuncture in urologic clinical setting as well as its proposed mechanisms of action and results. Medline database was assessed using isolated and conjugated key words (Chinese Medicine, Kampo, Chinese Herbal, Calculi, Stone Disease, Kidney, Acupuncture, Herbal Medicine). Articles were reviewed and summarized. Herbal medicine has been proven to be free from side-effects and therefore suitable for long term use therapy. Its antilithic beneficial effects include increased urinary volume, increased magnesium excretion (Takusya), inhibitory activity on calcium oxalate aggregation (Takusya, Wulingsan and Desmodyum styracyfolium), inhibition of calcium oxalate nucleation and hydroxyapatite internalization (Wulingsan). In contrast, acupuncture, has shown to be effective as a pre-treatment anxiolytic and analgesic during colic pain and extracorporeal shock wave lithotripsy treatment, reducing the need for complementary sedative drugs. Chinese traditional medicine is promising as regards its role in stone prevention. An effort must be made in order to standardize study protocols to better assess acupuncture results since each procedure differs in regards to selected acupoints, electrostimulation technique and adjunct anesthetics. Similarly, standardization of Kampo formulations and acceptable clinical endpoints (imaging vs. symptomatic events) is needed.
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Since hypercalciuria is a common feature of idiopathic calcium oxalate (CaOx) nephrolithiasis, renal epithelial cells of stone patients are exposed to various crystals in the presence of high calcium. This study was performed to determine the effect of high calcium levels on CaOx crystal-induced cell injury. We exposed human renal epithelial cell line, HK2 in vitro to CaOx monohydrate crystals at a concentration of 133 microg/cm(2) for 1, 3, 6 or 12 h in the presence or absence of 5 or 10 mM/L calcium Ca(++). We determined the release of lactate dehydrogenase as marker of injury and hydrogen peroxide (H(2)O(2)) and 8-isoprostane (8-IP) as sign of oxidative stress. Cells were also examined after trypan blue and nuclear DNA staining with 4',6-diamidino-2-phenylindole to determine their membrane integrity and apoptosis respectively. Exposure of cells to 5 or 10 mM/L of Ca(++,) for up-to 6 h, resulted in increased trypan blue and DAPI staining and production of H(2)O(2). Similarly an exposure to CaOx crystals also resulted in increased trypan blue and DAPI staining and H(2)O(2) production. An exposure to 5 mM/L Ca or CaOx crystals also resulted in increased production of 8-IP. A combination of the two treatments, Ca and CaOx crystals, did not show anymore changes than exposure to high Ca or CaOx crystals alone, except in the case of a longer exposure of 12 h. Longer exposures of 12 h resulted in cells sloughing from the substrate. These results indicate that exposure to high levels of Ca or CaOx crystals is injurious to renal epithelial cells but the two do not appear to work synergistically. On the other hand, results of our earlier studies suggest that oxalate and CaOx crystals work in synergy, i.e., CaOx crystals are more injurious in the presence of high oxalate. Perhaps Ox and CaOx crystals activate different biochemical pathways while Ca and CaOx crystals affect the identical pathways.
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Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals. The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats. Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone. The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.
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The inhibitory effects of hydrolyzable tannins, condensed tannins and related polyphenols on the activity of xanthine oxidase (XOD), catalyzing uric acid formation from xanthine, were investigated. Marked differences in the strength of the inhibition were observed. Some of the differences among the monomeric hydrolyzable tannins were due to their molecular weights, reflecting the number of phenolic hydroxyl groups in the molecule. However, the inhibitory activity of several oligomeric hydrolyzable tannins seemed particularly low in spite of their large molecular size. It was also observed that differences in location of acyl groups on the carbohydrate cores caused differences in the inhibitory activity among monomeric and oligomeric hydrolyzable tannins. A caffeic acid derivative (caffeetannin), 3,5-di-O-caffeoylquinic acid (24), also inhibited this enzyme. Galloylation and the degree of polymerization in proanthocyanidins were also shown to affect remarkably the strength of the inhibition. Among the compounds tested in the present study, valoneic acid dilactone (29), isolated from Mallotus japonicus, inhibited the enzyme most effectively. A kinetic study showed that this dilactone inhibited XOD non-competitively. Comparison of the inhibitory effect on XOD, with the binding activity to hemoglobin, for each tannin, suggests that their inhibition of XOD is not based on non-specific binding to the protein. Similar comparison of the inhibitory effect on XOD with the inhibitory effect on the generation of superoxide anion radical (O2-.) from the hypoxanthine-XOD system revealed that the inhibition of O2-. generation by tannins is due to their radical-scavenging activity, and not due to their inhibitory activity upon the enzyme.
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Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nucleate to form crystals of calcium oxalate monohydrate (COM), the most common crystal in renal stones. It is not known how these nascent crystals are retained in the nephron to form calculi in certain individuals. Recent studies from this laboratory indicate that COM crystals can bind within seconds to anionic, sialic acid-containing glycoproteins on the apical surface of kidney epithelial cells in culture, suggesting one mechanisms whereby crystals could be retained in the tubule. Adherence of crystals to renal epithelial cells is inhibited by specific urinary anions such as glycosaminoglycans, uropontin, nephrocalcin, and citrate, each of which binds to the crystalline surface. Thus competition for the crystal surface between soluble anions in tubular fluid and anions on the apical cell surface could determine whether or not a crystal binds to the cell. Once bound, crystals are quickly internalized by renal cells in culture; reorganization of the cytoskeleton, alterations in gene expression, and initiation of proliferation can then ensue. Each of these cellular events appears to be regulated by a different set of extracellular factors. Identification of molecules in tubular fluid and on the cell surface that modulate crystal-cell interactions, as well as their mechanism of action, appears critical for understanding the pathogenesis of nephrolithiasis.
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To ascertain diversity or similarity in stone prevention and problems among different countries around the world. Urolithiasis research groups from 10 countries completed a questionnaire. Cost of extracorporeal shock wave lithotripsy (ESWL) was considerably greater than that of drugs in four countries, and equivalent in remaining countries. Stone composition was similar among different countries. Certain urinary risk factors were associated with particular countries, probably from dietary indiscretions. ESWL was used in the majority of patients and open surgery in a minority of patients, except in one country. Medical diagnostic evaluation was used in the majority of patients except in one country. Drug treatment was nonselective, and provided to a minority of recurrent stone-formers. There is considerable similarity in stone presentations and problems throughout the world. The diversity is likely to be due to nutritional-environmental and socio-political-economic factors.
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The structure-activity relationship of flavonoids as inhibitors of xanthine oxidase and as scavengers of the superoxide radical, produced by the action of the enzyme xanthine oxidase, was investigated. The hydroxyl groups at C-5 and C-7 and the double bond between C-2 and C-3 were essential for a high inhibitory activity on xanthine oxidase. Flavones showed slightly higher inhibitory activity than flavonols. All flavonoid derivatives except isorhamnetin (30) were less active than the original compounds. For a high superoxide scavenging activity on the other hand, a hydroxyl group at C-3' in ring B and at C-3 were essential. According to their effect on xanthine oxidase and as superoxide scavengers, the flavonoids could be classified into six groups: superoxide scavengers without inhibitory activity on xanthine oxidase (category A), xanthine oxidase inhibitors without any additional superoxide scavenging activity (category B), xanthine oxidase inhibitors with an additional superoxide scavenging activity (category C), xanthine oxidase inhibitors with an additional pro-oxidant effect on the production of superoxide (category D), flavonoids with a marginal effect on xanthine oxidase but with a prooxidant effect on the production of superoxide (category E), and finally, flavonoids with no effect on xanthine oxidase or superoxide (category F).
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The plants of the genus Phyllanthus (Euphorbiaceae) are widely distributed in most tropical and subtropical countries, and have long been used in folk medicine to treat kidney and urinary bladder disturbances, intestinal infections, diabetes, and hepatitis B. In recent years, the interest in the plants has increased considerably. Substantial progress on their chemistal and pharmacological properties, as well as a few clinical studies of some Phyllanthus species have been made. This review discusses the current knowledge of their chemistry, the in vitro and in vivo pharmacological, biochemical, and clinical studies carried out on the extracts, and the main active constituents isolated from different species of plants of the genus Phyllanthus. These studies carried out with the extracts and purified compounds from these plants support most of their reported uses in folk medicine as an antiviral, in the treatment of genitourinary disorders, and as antinociceptive agents. However, well-controlled, double-binding clinical trials are lacking. Several compounds including alkaloids, flavonoids, lignans, phenols, and terpenes were isolated from these plants and some of them interact with most key enzymes. Together this data strongly supports the view that the plants belonging to the genus Phyllanthus have potential beneficial therapeutic actions in the management of hepatitis B, nefrolitiase, and in painful disorders.
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We investigated the in vitro effect of an aqueous extract of Phyllanthus niruri L. on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited a potent and effective non-concentration-dependent inhibitory effect on the CaOx crystal internalization. This response was present even at very high (pathologic) CaOx concentrations and no P. niruri L.-induced toxic effect could be detected. Biochemical analysis of culture media containing P. niruri L. did not provide any clues for the elucidation of the cellular pathways affected by this natural product. Although further studies are necessary for a better understanding of the role of P. niruri L. in urolithiasis, our findings show that this natural product could be an attractive alternative for the treatment of urinary stones.