2. ACTIVIDAD DEL SNS
2.1 N OTIFICACIONES R EGISTRADAS
Latin:Crataeva = Crateva. Crataeva magna (Lour) DC, C. religiosa var.
nurvala (Buch.-Ham.) Hook.f. & Thom.
Sanskrit: Varuna Hindi: Varun
Tamil: Maralingam
Crataeva nurvala (see Plate 9 in color gallery) is a deciduous tree found throughout India, well known for its handsome foliage and beautiful cream-colored flowers. The ash-gray stem bark is used in Ayurveda for treating urinary disorders both as a single drug and also in combination with other drugs. Thus, it has been used for the treat-ment of urinary stones, for benign prostatic hypertrophy (BPH), and for treating urinary infections. It is also used to improve appetite and is used both internally and externally to treat rheumatism. However, it is best known for its action on urinary calculi and it has an official status in the Indian Herbal Pharmacopoeia, 2002, as an anti-urolithiatic drug.1
The major constituent is the triterpene lupeol (0.6 percent), which has been shown to have antilithotriptic activity. Other constituents are the al-kaloids (cadabicine, cadabicine diacetate, and cadabicine dimethyl ether), minor flavonoids [(-)-catechin, (-)-epicatechin 5-glucoside, and (-)-epiafzelechin], sterols (diosgenin, -sitosterol, -sitosterol acetate,
lupeol acetate,␣-spinosterol acetate, ␣-taraxasterol, 3-epilupeol, lupe-none), triterpenes (betulinic acid, friedelin, varunol), flavonoids (rutin, quercetin), and the isothiocyanate glucoside—glucocapparin.1,2
Benign prostatic enlargement
The equivalent of benign prostatic enlargement or enlargement of the prostate gland leading to difficulty in passing urine is known as mutragranthi in Ayurveda (mutra: urine; granthi: knot or block).
Crataeva nurvala is considered useful in mutragatha or various ob-structive conditions of the urinary tract.2
The bladder function of ten dogs was studied using flow cystometry after treatment with Crataeva nurvala for 40 days, which showed a hypertonic effect against the initial values.3The ethanolic extract of Crataeva nurvala has shown anti-inflammatory activity in carrageenin-induced edema in experimental animals.4The petroleum ether extract of the stem bark has shown anti-inflammatory activity in acute, subacute, and chronic models of inflammation.5 In addition, lupeol was shown to exhibit anti-inflammatory effect.6, 7
In an open study on 30 patients with prostatic hypertrophy and re-sultant hypotonic bladder, 50 ml stem-bark decoction (prepared by boiling 1 part stem bark with 16 parts water, reducing to one-fourth and filtering) was given twice a day to patients and the bladder func-tion examined using cystometric studies. It was found that patients experienced improvement in bladder tone with consequent relief in symptoms such as frequency of urination, incontinence, pain, and re-tention of urine. The force in expulsion of urine was also found to in-crease. In patients exhibiting hypotonia and atonia after prostectomy, the decoction was found to increase bladder tone, whereas improve-ments were also seen in neurogenic bladder. The residual volume of urine decreases significantly.3
In an open study with 56 patients with enlarged prostate, 50 were on drug while 6 patients and 10 healthy subjects served as control. A total of 50 patients were treated daily with freshly prepared decoction of Crataeva nurvala stem bark as described above, dose in Indian measures of 4-6 tolas twice a day (5 tolas = 2 fluid ozs.) for a period of 6 months. Major presenting symptoms were retention of urine, dribbling, frequent micturition and burning, and difficulty in passing
urine. Most patients had mild renal insufficiency. The status of pa-tients was evaluated after 3-4 weeks, 3 months, and 6 months of ther-apy. Seventy percent of patients had complete relief in symptoms at the end of 6 months, whereas the remaining patients had considerable relief. Initially 56 percent of patients showed hypotonia, 36 percent showed hypertonia, and a mere 8 percent were normotonic. However, at the end of 6 months, 75 percent of patients were normotonic with normal residual urine, whereas 25 percent were hypotonic with resid-ual urine below 50 cc. The action of the drug was considered signifi-cant when compared to the small control group. This has been as-cribed to the action on the bladder musculature and to its anti-inflammatory activity.4
Urinary stones
Stones in the urinary tract are termed asmari in Ayurveda (asmam:
stone; ari: enemy; or enemy in the form of stone). There are different kinds of stones described in Ayurveda and comparison of the Ayurvedic descriptions with Western literature suggests that they correspond to differences in chemical composition.2
Decoction4, 8of Crataeva nurvala and extract9,10reduced signifi-cantly weight of stones in experimental animals. In calcium oxalate lithiasis, treatment with the decoction elevated levels of the oxalate-synthesizing liver enzyme glycolic oxidase and lowered the deposi-tion of stone-forming constituents in the kidney. In addideposi-tion, partial reversal of magnesium excretion prevented stone formation, since lower levels of magnesium tend to increase oxalate deposition.8The pentacyclic triterpene lupeol has been shown to possess antiuro-lithiatic properties in albino rats at a dose level of 50 mg⭈kg⫺1. Animals treated with lupeol showed reduced tendency to form stones, and very small stones were dissolved or flushed out.11Lupeol (25 mg⭈kg⫺1body weight) has been shown to reduce renal excretion of calcium oxalate and also to reduce renal tubular damage as seen by lowered levels of several urinary marker enzymes, which indicate re-nal tissue damage.12 In addition, lupeol has antioxidant activity, which contributes to its protective action against calculosis.13
In an open trial, 46 patients with urinary stone were treated with 50 ml of stem-bark decoction of Crataeva nurvala administered twice a day for varying periods. It was found that 28 patients were spontaneously able to pass the stone in 1-47 weeks, whereas 18 pa-tients had considerable relief in symptoms. The average time for passing the stones was 16 weeks for all except two patients who needed 36 and 47 weeks. The process of expulsion of the stone may be both due to the action of the drug in reducing the stone size and its action on the smooth muscle.3
A study of urinary electrolytes after 1 month of treatment with C.
nurvala was found to alter the relative proportion of urinary electro-lytes involved in calculus formation. Excretion of urinary calcium was greatly reduced, although that of sodium and magnesium was significantly increased. In addition, crystalurea was found reduced in 75 percent of patients.3
Another trial was carried out with 55 patients (calcium oxalate stones) in group A, 15 patients (calcium phosphate nephrolithiasis) in group B, and a control group (20 subjects). The decoction of the stem bark was given to patients for 12 weeks resulting in considerable re-duction in pain (70.90 percent in group A; 73.33 percent in group B), and dysuria (63.63 percent in group A; 53.84 percent in group B), whereas some patients experienced radiological reduction in the size of stones (33.33 percent in group A; 35.72 percent in group B).14
Urinary infection
Urinary tract infection (UTI) is a very commonly found condition, and is generally of bacterial origin. Based on symptoms, UTI has been correlated with mutrakrichhra vyadhi in Ayurveda. Symptoms include discomfort associated with urination.15
In vitro studies showed that Crataeva nurvala extract showed anti-bacterial activity against strains causing urinary infections.16
In an open trial, Crataeva nurvala decoction was given to patients suffering from urinary tract infection for 4 weeks. There was relief in symptoms and absence of pus cells together with negative cultures in some patients; however, 68 percent continued to test positive for in-fection even while experiencing relief of symptoms.3
In a study, 84 patients with UTI were treated with stem-bark de-coction of Crataeva nurvala. Of the 84 patients 55 percent had com-plete relief and 40 percent showed improvement.17
Thus Crataeva nurvala has several useful properties for urinary tract disorders combined together in one drug and deserves further studies to fully exploit its properties.
The decoction of stem and root bark are well tolerated.18
NOTES
1. Indian herbal pharmacopoeia (rev. new edn., pp. 153-160). Mumbai: Indian Drug Manufacturers’ Association, 2002.
2. Prabhakar YS, Suresh Kumar D. Crataeva nurvala: An Ayurvedic remedy for urological disorders. Br J Phytother 4(3):103-109 (1997).
3. Deshpande PJ, Sahu M, Kumar P. Crataeva nurvala Hook and Forst.
(varuna)—The Ayurvedic drug of choice in urinary disorders. Indian J Med Res 76 (suppl. December):46-53 (1982).
4. Effects of varuna (Crataeva nurvala Buch.-Ham.) in enlarged prostate, asso-ciated urinary disorders (pp. 37-39, 8-29). New Delhi: Central Council for Re-search in Ayurveda and Siddha, Ministry of Health & Family Welfare, Government of India, 1987.
5. Das PK, Rathor RS, Lal R, Tripathi RM, Biswas M. Anti-inflammatory and antiarthritic activity of varuna. J Res Indian Med 9:9-16 (1974).
6. Singh S, Bani S, Singh GB, Gupta BD, Banerjee SK, Singh B. Anti inflam-matory activity of lupeol. Fitoterapia 68:9-16 (1997).
7. Geetha T, Varalakshmi P. Anti-inflammatory activity of lupeol and lupeol linoleate in adjuvant-induced arthritis. Fitoterapia LXIX:13-19 (1998).
8. Varalakshmi P, Shamila Y, Latha E. Effect of Crataeva nurvala in experi-mental urolithiasis. J Ethnopharmacol 28:313-321 (1990).
9. Anand R, Patnaik GK, Jain P, Kulshreshtha DK, Srimal RC, Dhawan BN.
Anti-urolithiatic activity of Crataeva nurvala in albino rats. Indian J Pharmacol 22:23-24 (1990).
10. Anand R, Patnaik GK, Kulshreshtha DK, Mehrotra BN, Srimal RC, Dhawan BN. Anti-urolithiatic activity of Crataeva nurvala ethanolic extract on rats.
Fitoterapia 64:345-350 (1993).
11. Anand R, Patnaik GK, Kulshreshta DK, Dhawan BN. Anti-urolithiatic activ-ity of lupeol, the active constituent isolated from Crataeva nurvala. Phytother Res 8:417-421(1994).
12. Malini MM, Baskar R, Varalakshmi P. Effect of lupeol, a pentacyclic triterpene, on urinary enzymes in hyperoxaluric rats. Jpn J Med Sci Biol 48:211-220 (1995).
13. Baskar R, Meenalakshmi Malini M, Varalakshmi P, Balakrishna K, Bhima Rao R. Effect of lupeol isolated from Crataeva nurvala stem bark against free radi-cal induced toxicity on experimental urolithiasis. Fitoterapia 67:121-125 (1996).
14. Singh RG, Usha, Kapoor S. Evaluation of the antilithic properties of varun (Crataeva nurvala): An indigenous drug. J Res Edu Indian Med 10(2):35-39 (1991).
15. Reddy RG. Combating UTI in Ayurveda. Express Pharma Pulse (August 9):21 (2001).
16. Chandra S, Gupta CP. Antibacterial activity of medicinal plant Crataeva nurvala (bark) against bacterial strains causing urinary tract infection. Asian J Chem 13:1181-1186 (2001).
17. Kumar P, Singh LM, Deshpande PJ. Clinical study with Crataeva nurvala in urinary tract infection. J Sci Res Plants Med 3(2&3):75-79 (1982).
18. Selected medicinal plants of India. A monograph on identity, safety and clini-cal usage (pp. 108-111). Bombay: Chemexcil. Basic Chemiclini-cals, Pharmaceuticlini-cals and Cosmetics Export Promotion Council, 1992.