Dr. S Sooranna, Ms J Hirani, Ms. N Khan* and Dr. I Das* Academic Departments of Obstetrics & Gynaecology and Psychiatry, *Charing Cross & Westminster Medical School, Chelsea & Westminster Hospital, London.
Several properties of garlic (Allium sativum L,) can be attributed to its ability to physiologically increase nitric oxide (NO)(1). NO is produced from arginine by NO synthase (NOS) which can exist in both constitutive (calcium-dependent, caNOS) and inducible (calcium-independent: ciNOS) isoforms (2). Tetrahydrobiopterin, an essential co-factor for NOS, is synthesised from GTP by GTP cyclohydrolase 1 (GTPCH-I). The many actions of NO include inhibitor of platelet aggregation and lowering of blood pressure. When too little NO is produced by the body, this can lead to hypertension, angina and impotence. Overproduction of NO can result in circulatory shock, stroke and inflammation (3) Recent studies have shown that NOS activities are decreased in placental tissues of pregnancies complicated by pre-eclampsia and growth retardation (4)
In order to explore the interactions of garlic with the arginine- NO pathway during pregnancy we have used cell free homogenates of placental tissue, cultured cell lines characteristic of placental trophoblast and 1-2mm 3 pieces of placental villous tissue and incubated these with extracts of garlic. In vivo studies were performed by administering garlic tablets to patients for several days prior to undergoing termination of pregnancy and then measuring blood flow within the uterine arteries prior to the operation as well as measuring placental NOS activities.
Our results suggest that garlic can increase NOS activity both in cells and in cell-free systems. The activity of caNOS increases several-fold upon addition of garlic extract to freshly prepared cell-free homogenates of placental villi. Although arginine (the precursor of NO) is present in garlic, the activation of caNOS is independent of this substrate. The activation is partially abolished when garlic is heated but is unaffected by perchloric acid treatment. Both NOS and GTPCH-1 activities are increased by incubation of choriocarcinoma cells with garlic, and this effect is probably due to activation of the inducible isoforms. Low concentrations of garlic can also increase polyamines (which are also produced from arginine via the enzyme ornithine decarboxylase)(5) within these cells and these substances promote growth and cellular differentiation. When pieces of placental tissue were incubated with extracts of garlic, this also caused increased NOS activity.
Results from our in vivo studies are on-going and as yet inconclusive. Doppler flow measurements of the resistance index (RI) and pulsatility index (PI) of the uterine arteries normally decrease throughout gestation. This reflects the increase in blood flow as pregnancy progresses. Administration of garlic tablets during the first trimester of pregnancy appears to decrease both R1 and P1, such that patients appear to be further on in their pregnancy. Placental tissue NOS activities and polyamine concentration do not appear to be affected by administration of garlic.
The ability of garlic to increase NOS in several experimental systems supports to the claim that
garlic can exert some of its therapeutic properties by increasing NO production in the body. Our
results suggest that garlic may help to alleviate complex pathophysiological conditions such as pre-
eclampsia and growth retardation. Also,
preliminary studies(6) , have suggested that NO donors may arrest the initiation of pre-term labour
and garlic may similarly prove to be of use in women at risk from this condition.
References
1.Das et al, Curr. Med. Res. Opi. 1995; 13: 257-263/).
2. S. Moncada et al. Pharm. Rev. 1991; 43: 109-142).
3. E.Anggdrd, Lancet, 1994; 343: 1199-1206).
4. N.H.Morris et al, Br. J. Obstet. Gynaecol. 1995; In press).
5. D.Morgan. Essays Biochem. 1987; 23: 82-115/)
6. Lees et al, Lancet, 1994; 343: 1325-1326)