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Saraca asoca (Roxb.) de Wilde

S. asoca is a rainforest tree with beautiful foliage and fragrant, orange-yellow flowers. It is an erect, evergreen tree, with deep green leaves growing in dense clusters. The flowers are borne in heavy,

Inflorescence of 5. asoca. Reproduced with permission from Dr D. Suresh Baburaj, Ooty

FIGURE 5.7 Inflorescence of 5. asoca. Reproduced with permission from Dr D. Suresh Baburaj, Ooty.

lush bunches and turn red before wilting (Figure 5.7). It is reputed to cure dysfunctional bleeding (Warrier et al. 2008). Interestingly, in Ayurveda the bark of the tree is used only in the treatment of gynecological disorders.

S. indica is the major ingredient of the ayurvedic medicine Asoka arista indicated in menorrhagia, metrorrhagia, leucorrhea, primary amenorrhea, subfertility and menstrual disorders in general (Middelkoop and Labadie 1983). Women suffering from dysfunctional menorrhagia and menorrhagia caused by the use of an intra-uterine contraceptive device showed abnormally high levels of PGE2 and PGFa in their endometrial tissue, as reported by Willman et al. (1976), who measured the concentrations of prostaglandins by radioimmunoassay in samples of endometrial tissue from 155 women. Lindner et al. (1980) examined the role of prostaglandins in three pivotal events of the female reproductive cycle - ovulation, luteolysis, and menstruation. They concluded that PG-synthase inhibitors can find useful applications in the management of menstrual disorders, such as functional dysmenorrhea and menorrhagia. As the bark of S. asoca is the main ingredient in Asoka arista, Middelkoop and Labadie (1985) tested extracts and pure compounds found in this bark for their influence on the PGH2 synthase activity in vitro.

Extracts of S. asoca bark and pure compounds isolated from the bark were tested for properties that might inhibit the conversion of arachidonic acid by the PGH, synthase. They were assayed spectrophotometrically, with adrenaline as cofactor. Methanol- and ethyl acetate extracts of S. asoca inhibited the conversion and the observed inhibition was confirmed in an oxygraphic assay. Two procyanidin dimers from the ethyl acetate extract showed enzyme-catalyzed oxidation in the assay. The ether extract of the bark was also found to contain substances which were capable of being oxidized by the PGH, synthase. The holistic action of the components of the bark may explain the mode of action of S. asoca (Middelkoop and Labadie 1985)

Leucorrhoea is caused by bacterial or fungal infections in the mucous membranes of the vagina. Therefore, an effective medicine against it should have bactericidal and fungicidal activity or should be able, especially in the case of a fungal infection, to lower the pH of the mucous membranes (Spence and Melville 2007). Chloroform, methanol, aqueous and ethanol extracts of the stem bark of 5. indica were investigated for their antibacterial and antifungal activities against standard strains of the bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, Klebsiella pneumoniae, Proteus mirabilis, Salmonella typhimurium, Streptococcus pneumoniae and the fungi Candida albicans and Cryptococcus albidus. Methanol and aqueous extracts exhibited antimicrobial activity with MIC ranging from 0.5-2% and 1-3% respectively. Methanol extract exhibited the strongest activity against both bacteria and fungi (Sainath et al. 2009).

It can be assumed that the mild oxytocic effect of a drug could stop the uterine bleeding by constriction of the blood-vessels in the myometrium. This effect can be assayed by measuring in vitro the direct uterine activity of the drug. Satyavati et al. (1970) reported marked uterine stimulating activity of S. indica in vitro.

Strychnos potatorum L. f.

S. potatorum is a deciduous tree. The seeds of the tree are commonly used in Ayurveda, as well as for purifying water (Figure 5.8) (Warrier et al. 2008). No clinical studies have been reported for the anti-diabetic activity of S. potatorum. However, a few studies indicate that the herb has the ability to regulate blood glucose levels. Dhasarathan and Theriappan (2011) investigated the anti-diabetic activity of 5. potatorum seeds. A diabetic state was induced in Wistar albino rats by intraperitoneal injection of alloxan at a dose of 100 mg/kg of body weight. Treatment with alloxan reduced body weight and liver weight. The blood glucose level dropped by 53% with extract treatment, demonstrating the anti-diabetic potential of the plant. Serum enzymes A.S.T. and A.L.T. were increased from 24 and 18 IU/1 to 60 and 65 IU/1 respectively, whereas A.L.P. was reduced to 5 IU/1 from 14 IU/1. The total serum protein level also increased up to 5 mg/ml in extract-treated animals. The insulin level showed an increase of up to 61 pg/ml within 30 days of extract treatment compared to controls. The plant extract lowered the initial cholesterol level of 219 pg/ml to 170 pg/ml. In liver, the A.S.T., A.L.T. and A.L.P. enzymes were decreased significantly (Dhasarathan and Theriappan

2011).

The anti-diabetic effect of seeds of S. potatorum Linn, was further evaluated in a model of diabetes mellitus using streptozotocin (Biswas et al. 2012). Changes in fasting blood sugar were monitored periodically for 12 weeks along with weekly measurement of body weight, food and water intake for 4 weeks. The anti-diabetic effects were compared with glipizide as the reference hypoglycemic drug. S. potatorum Linn. (100 mg/kg p.o.) significantly reduced fasting blood sugar, the effects being comparable with glipizide (40 mg/kg, p.o.), which is an established hypoglycemic drug. The herb also increased body weight in streptozotocin-induced diabetic rats. Biswas et al. (2012) remark that, as the development of diabetes by streptozotocin is related to increased generation of free radicals (Van Dyke et al. 2010), it is possible that the observed anti-diabetic effect is mediated, at least partly, through its antioxidant effect. Previous studies have demonstrated the anti-arthritic, anti-inflammatory and antioxidant activity of S. potatorum Linn. (Ekambaram et al. 2010), which may be attributed to the presence of antioxidants such as flavonoids and phenols (Mallikharjuna et al. 2007). The available research reports indicate that S. potatorum has promising anti-diabetic activity meriting further pharmacological studies.

Tabernaemontana divaricata (L.) R.Br. ex Roem. & Schultes

T. divaricata is an evergreen shrub native to India. It is now cultivated throughout South-East Asia and the warmer regions of continental Asia. The plant generally grows to a height of 5-6 feet and the large shiny leaves are deep-green in color. The waxy flowers are found in small clusters on the stem tips. The flowers appear sporadically throughout the year (Figure 5.9). The roots have a bitter taste. It is used in the treatment of eye diseases and diabetes mellitus (Warrier et al. 2008).

The leaves are rich in alkaloids like conophylline, conophyllidine (Kam et al. 1993), voaphylline, /Vrmethylvoaphylline, voaharine, pachysiphine, apparicine, (- )-mehranine, conofoline (Kam and Anuradha 1995), taberhanine, voafinine, (V-methylvoafinine, voafinidine, voalenine and conophyl- linine (Kam et al. 2003).

Fujii et al. (2009) studied the anti-diabetic effects of conophylline in rats by oral administration. Crude conophylline-containing extracts were prepared from the leaves of T. divaricata and administered to both normal and streptozotocin-induced diabetic Sprague Dawley rats. Conophylline was orally absorbed and showed an increase in its plasma level in normal and diabetic rats. After a single oral administration, the plasma conophylline concentration reached its maximum from 1.5 h to 3 h and gradually decreased in 24 h. The alkaloid lowered the blood glucose level and increased the plasma insulin level in the diabetic rats after daily administration for 15 days. Rats treated with conophylline at 0.11 and 0.46 mg/kg/day had fasting blood glucose levels of 411 ± 47 and 381 ±65 mg/dl, respectively; while the glucose level of control rats was 435 ± 46 mg/dl. The fasting blood glucose levels in Goto-Kakizaki rats were also decreased by conophylline in a dose-dependent manner after repetitive administration for 42 days. (The Goto-Kakizaki rat is a model for type 2 diabetes, bred from non-diabetic Wistar rats selected from a normal population with a glucose tolerance response slightly deviating from the normal range (Goto et al. 1975)). These results suggest that the extract from conophylline-containing plants like T. divaricata may be useful in the treatment of type 2 diabetes mellitus.

Conophylline is also reported to increase the (3-cell mass in neonatal streptozotocin-treated rats (Kodera et al. 2009). Streptozotocin (S.T.Z., 100 pg/g) was injected into neonatal rats, and then conophylline (2 pg/g) was administered to them for 1 week. In neonatal S.T.Z. rats treated w'ith control solution, the plasma glucose concentration increased for several days, and after 8 weeks the plasma glucose concentration was very high compared to that of normal rats. The glucose response to intraperitoneal glucose tolerance test was significantly reduced in neonatal S.T.Z. rats treated with conophylline. The [3-cell mass and the insulin content of the pancreas were also significantly increased in the conophylline group.

Reduction of the p-cell mass is crucial to the pathogenesis of diabetes mellitus. Therefore, the discovery of bioactives, which induce differentiation of pancreatic precursors to (3- cells, could be a new approach to treat diabetes. To identify such agents, Kojima and Umezawa (2006) screened many compounds, using pancreatic AR42J cells, a model of pancreatic progenitor cells. They found that conophylline, originally extracted from leaves of Ervatamia microphylla and present in T. divaricata too, was effective in converting AR42J into pancreatic |3-cells. The differentiation-inducing activity of conophylline is very similar to that of activin A. However, unlike activin A, conophylline does not induce apoptosis. Conophylline also causes differentiation of cultured pancreatic precursor cells obtained from fetal and neonatal rats (Kojima and Umezawa,2006; Sidthipong et al. 2013).

Kanthlal et al. (2014) investigated the anti-diabetic effect of aerial parts of T. divaricate and their ability to prevent oxidative stress in alloxan-induced diabetic rats. Two doses of methanol extract of aerial parts of T. divaricata (100 and 200 mg/kg, per os.) were tested in alloxan-diabetic rats. Administration of a 200 mg/kg dose attenuated the increased level of glucose produced by alloxan. The extract also alleviated the effect of the oxidative damage similar to the standard drug glibenclamide.

 
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