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A standardized natural extract offers comprehensive urinary health support

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 A standardized PHYTOPHARMACEUTICALS

natural extract offers

comprehensive
urinary health
support and more…
INTRODUCTION
MUHAMMED MAJEED 1
LAKSHMI PRAKASH 2
Crataeva nurvala Buch-Ham. (Syn.
Crataeva religiosa Frost.) (Fam. Sabinsa Corporation
Capparidaceae) is an evergreen tree that 70 Ethel Rd. West, Suite 6
Piscataway, NJ 98854, USA
is indigenous to South India. Although it
Tel +1-732-777-1111
is known by different names throughout
Fax +1-732-777-1443
India, it is commonly identified by its www.sabinsa.com
Sanskrit name, Varuna. In Ayurvedic
medicine, Varuna is valued for its 1. mmajeed@sabinsa.com
benefits in the management of urinary
2. lprakash@sabinsa.com
and inflammatory disorders (1,2).
Pharmacological studies using the root
bark and stem bark of C. nurvala, in
recent years, have confirmed its
beneficial effects in supporting the
management of urinary disorders,
including urolithiasis, and revealed its
potential benefits in supporting the
management of inflammatory
conditions, such as arthritis. Cratavin®*
is a standardized extract containing a
minimum of 1.5% w/w of lupeol,
prepared from the bark of Crataeva
nurvula.

BOTANICAL ASPECTS

Crataeva nurvala is a moderate sized

deciduous tree. The mature bark is
typically 6-15 cm long and 3-10 cm
wide with a thickness varying from
5-15 mm. The outer surface of the bark published by srl
is gray to grayish-brown and rough due Via Cesare da Sesto, 10
to the presence of several small and
rounded lenticels. The inner surface is
20123 Milano - Italy
smooth and whitish-brown to buff Tel. 0039 02 83241119
Fax 0039 02 8376457
Figure 1 – Some chemical constituents of w w w . b5 s r l . c o m
* A trademark of Sabinsa Corporation Crataeva nurvala (“Varuna”) extract

PHYTOPHARMACEUTICALS NOVEMBER/DECEMBER 2007 3

 obstructive – e.g. urolithiasis the C. nurvala-treated group had
(“stones” in the urinary reduced edema, ulceration and cellular
system) and prostatic infiltration than rats of the control
hypertrophy – or non- group (14).
obstructive – e.g. infection of The results of another animal model
the urinary tract and study indicated that C. nurvala is an
neurogenic bladder (14). important regulator of oxalate synthesis.
Urinary stones form from As shown in Figure 2, C. nurvala
the deposition of various stone reduced the levels of stone forming
forming, urinary constituents in constituents, calcium, oxalate, and
the renal tissues. People with a phosphorous, in the kidneys of stone
family history of urinary tract forming/treated rats (Group IV)
Figure 2 – Effect of C. nurvala on stone forming stone disease are more compared to the untreated/stone
constituents in the kidney tissue of stone forming and susceptible to developing formers (Group II) (15).
normal rats (15).
urolithiasis. The most common In addition, C. nurvala significantly
Values are expressed as the mean SD (n=6).
Comparisons were made between groups: a I & II; stone forming constituents are increased the magnesium levels of the
b I & III; c I & IV; d II & IV; and e III & IV. calcium with either oxalate or stone forming/treated rats (Group IV)
Group I: (normal controls) fed a standard diet for phosphate. Urinary tract compared to the stone forming controls
40 days; Group II: standard diet mixed with 3%
infections, kidney disorders, (Group II) that had low magnesium
gycolic acid for 40 days; Group III: standard diet for
40 days + C. nurvala decoction for the last 10 days; and metabolic disorders have levels (Figure 3). Magnesium is an
and Group IV: standard diet mixed with 3% glycolic been linked to stone important inhibitor of crystal growth,
acid for 40 days + C. nurvala decoction for the last formation. For example, and it has considerable solubilizing
10 days
calcium oxalate stones are power. Increased magnesium levels are
colored. Leaves are trifoliate. Flowers attributed to disorders such as associated with a lower Ca/Mg
are white or cream colored. Fruits have absorptive hypercalciuria, the absorption ratio (15).
multiple seeds and ovoid berries, and of too much calcium from food, and In a follow-up study, the researchers
seeds are embedded in the yellow, hyperoxaluria, the defective regulation (16) examined the effects of the
fleshy pulp of the fruits (1,2). of oxalate synthesis that causes C. nurvala decoction on certain
excessive excretion of the salt oxalate. biochemical constituents in the small
In each case, the excess constituent intestinal tract tissues of rats.
PHYTOCHEMISTRY cannot be dissolved in the urine. Thus, The results revealed that C. nurvala
it settles out as crystals and forms has a laxative effect similar to
Fatty acids, sugars, amino acids, stones (28-30). conventional drugs, bisacodyl and
flavones, sterols, and triterpenes have Surgery is the conventional method phenolphthalein, that seems to be
been isolated and identified in the root for removing urinary stones. However, mediated by the inhibition of Na+
bark of C. nurvala (5,8,9). Triterpenoids, surgery does not cure urolithiasis. Stone reabsorption in the intestinal epithelial
lupeol and varunol, have been isolated formation persists in the patient and cells via the inhibition of the enzyme,
from the root and stem bark (6). stones recur. Similarly, antibiotics may
According to the Indian Herbal be used to treat urinary tract
Pharmacopoeia, the major chemical infections; however, the infection may
constituent of the root bark is lupeol (1) recur due to the resistance of the
(Figure 1). Other major constituents of organisms to antibiotics.
the root bark include lupeol acetate, Preclinical and clinical studies have
α-spinasterol acetate, ψ-taraxasterol, shown that the stem and root bark of
3-epilupeol, and β-sitosterol (3,4). C. nurvala promote a healthy urinary
Lupenone (3,4), β-sitosterol acetate system. C. nurvala is beneficial in the
(3,4), and a pentacyclic triterpene management of urinary tract stone
alcohol, [Lupa-21,20 (29) diene-3β-ol] disease and other urinary disorders
(10), are also present in the root bark. such as urinary tract infection. Thus, it
Alkaloids, cadabacine and cadabacine may be an alternative to conventional Figure 3 – Effect of C. nurvala on the urinary
excretion of Calcium and the Ca/Mg ratio in
diacetate (11), flavonoids, (–)-catechin, antiurolithic drugs and
stone forming and normal rats (15).
(–)-epicatechin-5-glucoside, and antibiotics (14). Values are expressed as the mean SD (n=6).
(–)-epiafzelechin (12), and an For example, in a controlled Note: Calcium (Ca) levels are expressed as
isothiocyanate glucoside, glucocapparin animal model study wherein rats with mg Ca/24 h/rat. Comparisons were made
between groups: a I & II; b I & III; c I & IV;
(13), have been identified in the stem induced urolithiasis were tested, the
d II & IV; and e III & IV. Group I: (normal
bark. Flavonoids, rutin, quercetin, and urinary stone weights in rats treated controls) fed a standard diet for 40 days;
isoquercetin, have been isolated from with C. nurvala were significantly less Group II: standard diet mixed with 3% gycolic
the leaves (7). than those of untreated controls. In acid for 40 days; Group III: standard diet for
40 days + C. nurvala decoction for the last
Diseases of the urinary system affect addition, histopathological
10 days; and Group IV: standard diet mixed
the kidneys, ureters, bladder and examination of the rats’ bladder with 3% glycolic acid for 40 days + C. nurvala
urethra, and they are classified as mucosa on the 20th day showed that decoction for the last 10 days

4 NOVEMBER/DECEMBER 2007 PHYTOPHARMACEUTICALS

 water extract of C. nurvala alkylating agent widely used in cancer
increased the tone of smooth chemotherapy, is implicated in fatal
muscle of the intestine and cardiotoxicity through inducing oxidative
ureters in guinea pigs, dogs, stress. Lupeol and its ester were shown
and humans in vitro. Also, it to have an antioxidant protective effect
increased the tone of skeletal against CP induced cardiotoxicity in
muscle in frog rectii in vitro. Das animal models (32). Similar antioxidant
et al. (24) reported that the protective effects against nephrotoxicity
petroleum ether extract of due to cisplatin were also
C. nurvala bark inhibited the reported (33).
acute, subacute, and chronic
inflammations induced in albino
rats by carrageenin, histamine, CLINICAL STUDIES
croton oil, and formaldehyde.
C. nurvala extract’s anti- Clinically, C. nurvala was beneficial in
inflammatory activity was similar the management of chronic urinary
to the conventional drug, tract and neurogenic bladder infections,
betamethasone, but minus the calculi, and prostatic hypertrophy.
Figure 4 – Changes in the mean total bladder
capacity in non-operated and operated patients with side effects.
hypotonic bladders before and after treatment with Adjuvant arthritis induced in Prostatic Hypertrophy and Bladder
C. nurvala (14). animal models is similar to the Tone (14)
n=5 for non-operated and operated groups. In the
rheumatoid arthritis that A decoction of C. nurvala was
operated cases of hypotonic bladder, the mean total
bladder capacity was 766 before the operation humans experience (25). administered to patients in the form of
Arthritis involves the damage a decoction prepared from the stem
(Na+,K+)-ATPase. In addition, C. nurvala and inflammation of joints and bark of C. nurvala. Patients suffering
considerably reduced DNA and RNA associated tissues, and free radicals are from prostatic hypertrophy with
levels in treated/stone forming rats implicated in the pathogenesis of hypotonic bladder received 50 ml of
(Group IV) in comparison to stone rheumatoid arthritis. One group of the C. nurvala decoction twice daily.
forming controls (Group II). DNA researchers (26) studied the effects of (Hypotonic bladder due to prostatic
content gives an index of the number of lupeol and its ester lupeol linoleate hypertrophy is characterized by a
cells, and it is suggestive of atrophy against free radicals generated during marked increase in the total bladder
(shrinkage) of tissues. Thus, an increase complete Freud’s adjuvant-induced capacity.)
in DNA content observed in the stone arthritis in rats. Both lupeol and lupeol The following results were observed
forming control rats in this study linoleate restored the levels of after treatment with the C. nurvala
indicates tissue shrinkage. In contrast, antioxidant enzymes closer to normal decoction:
the herbal decoction did not influence control levels. Similarly, values for – The symptoms, frequency of
the nucleic acid levels in normal reduced glutathione in the blood were urination, incontinence, pain, and
animals (Group III) (16). restored closer to normal control values retention of urine, significantly
Other researchers found that when arthritic rats were treated with improved.
supplementation with lupeol, the marker lupeol and lupeol linoleate (26). – The expulsive force of urination was
active in C. nurvula extract, reduced the In a later study, researchers (27) increased.
levels of urinary oxalate and studied the effects of lupeol, lupeol – Bladder tone improved significantly.
considerably lowered the release of linoleate, and indomethacin, a known In addition, the volume of residual
Lactate dehydrogenase (LDH), another anti-inflammatory drug, in adjuvant- urine was reduced.
major oxalate-synthesizing enzyme, in induced arthritic rats. Lupeol linoleate Improvement in bladder tone and other
hyperoxaluric/treated rats compared to was more effective than either functions was also observed in cases of
hyperoxaluric controls. The authors unesterified lupeol or indomethacin in persistent hypertonia of the bladder in
noted lupeol was effective in reducing reducing footpad thickness and patients who received surgery and
the levels of various enzymes. This complement activity. It was concluded
protective effect may be attributed to its that the anti-inflammatory activity of the Table I – Sample Actives Blend for
diuretic activity that facilitates regular triterpenes, lupeol and lupeol linoleate, functional beverage formulation for Urinary
excretion of oxalate. This in turn reduces was attributed to their Health Support
saturation of oxalate in the renal tissues, anticomplementary activity. Recent
thereby minimizing cellular injury (17). studies revealed that lupeol suppresses
T-lymphocyte activity as well. Oral
administration of lupeol at doses of
ARTHRITIS AND 12.5-200 mg/kg p.o. inhibited CD4+ T
CARDIOVASCULAR HEALTH and CD8+ T cell counts and cytokines
SUPPORT IL-2, IFN-gamma (Th1) and IL-4
(Th2) (31).
Early studies (23) reported that the Cyclophosphamide (CP), an

PHYTOPHARMACEUTICALS NOVEMBER/DECEMBER 2007 5

those who did not after 3 months of who received a 4-week treatment of 7) FANG-KAI HO, YU PAN CHEM J. Taiwan
C. nurvala therapy as shown in C. nurvala were symptom free and their Pharm. Assoc. 1958, 10, 14-20 (cited in
Figure 4 – Hypotonia, the state of urine was devoid of microorganisms Ref.2)
reduced tension in muscles, may occur and pus cells. The authors concluded 8) LAKSHMI V., CHAUHAN J.S. Ind. Chem.
as a complication of pelvic swellings that the anti-inflammatory of C. nurvala Soc. 1974, 11, 1058 (cited in Ref.10)
(e.g. ovarian cyst or fibroid tumor), and and tonic effect on the smooth muscle 9) CHAUHAN J.S., et al. Indian Oil and Soap
it may persist even after the tumor is helps to evacuate the bladder of urine; Journal (Calcutta, India) 1972, 288
surgically removed. Similarly, C. nurvala and that if proper drainage is (cited in Ref.10)
therapy furnished beneficial effects in maintained for a long period of time, 10) LAKSHMI V., CHAUHAN J.S. Planta Medica
cases of neurogenic bladder and post- infection may be mitigated (14). 1977, 32, 214-6
prostatectomic atony of the bladder. 11) AHMED V.V., et al. J. Nat. Prod. 1987,
50, 1186 (cited in Ref.1)
Urinary Stones POTENTIAL HEALTH 12) SETHI V.K., et al. Phytochemistry 1984,
A decoction of C. nurvala (50 ml twice APPLICATIONS 23, 2402 (cited in Ref.1)
daily) was administered to patients with 13) KJAER A., THOMSEN H. Acta Chem.
urinary stones. After one month of Cratavin®, is thus beneficial as an Scand. 1962, 16, 783 (cited in Ref.1)
receiving the decoction, urinary adjuvant to Saw palmetto and other 14) DESHPANDE P.J., et al. Ind. J. Med. Res.
electrolytes were estimated and natural extracts in prostate health 1982, 76 (Suppl.), 46-53
compared with initial values. Treatment support, and can be used with 15) VARALAKSHMI P., et al. J.
with C. nurvala shifted the relative cranberry juice solids/extract and other Ethnopharmacology 1990, 28, 313-21
proportion of urinary electrolytes, natural agents in the management of 16) VARALAKSHMI P., et al. J.
particularly those that participate in urinary tract infections. The extract also Ethnopharmacology 1991, 31, 67-73
calculus formation, towards the non- offers anti-inflammatory benefits in joint 17) MALANI M.M., et al. Jpn. J. Med. Sci.
lithogenic (avoid stone formation) zone. health and cardiovascular support Biol. 1995, 48, 211-20
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electrolytes, C. nurvala seemed to would help to reduce the appearance diuretic activity of lupeol, the active
effect a 75% cure in patients with of wrinkles and is useful in “anti-aging” constituent isolated from Crataeva
crystalurea (a disease that increases the support formulations. nurvala Buch Ham. Proc. 24th Indian
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73 patients, 27 received surgery and yield about 20 tablets (servings). Each 1967, 40, 155 (cited in Ref.14)
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6 NOVEMBER/DECEMBER 2007 PHYTOPHARMACEUTICALS

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