s-allylcysteine and Hypertension

Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cysteine; Disulfides; Garlic; Humans; Hypertension; Phytotherapy; Plant Extracts; Sulfinic Acids

Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose-response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension.. A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose-response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire.. Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (-7.4±4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily.. Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Capsules; Combined Modality Therapy; Cysteine; Dietary Supplements; Double-Blind Method; Female; Garlic; Humans; Hypertension; Intention to Treat Analysis; Male; Middle Aged; Patient Compliance; Patient Dropouts; Plant Extracts; Plant Roots

The purpose of the present study was to investigate the role of fresh garlic homogenate (FGH) and its bioactive sulphur compound S-allyl cysteine sulphoxide (SACS) in potentiating antihypertensive and cardioprotective activities of captopril in rats. SACS was extracted from the fresh garlic using ion exchange resins with yield of 890 mg/kg garlic. The dose of SACS was calculated based on the amount of SACS extracted from 125 to 250 mg of FGH. Albino rats weighing 150-200 g were fed with 10% fructose in fluid for 3 weeks for induction of hypertension and subsequently administered FGH (125 and 250 mg/kg, p.o.) or SACS (0.111 and 0.222 mg/kg/day, p.o.) for the next 3 weeks in their respective groups. In CAP alone and interactive groups (GH+CAP; SACS+CAP), captopril 30 mg/kg was given during sixth week of 10% fructose in fluid. At the end of drug treatment, animals were given isoproterenol 175 mg/kg subcutaneously for two consecutive days. Additionally, varying concentrations of SACS (4, 8, 16, 32 and 64 ng), CAP (1, 2, 4, 8 and 16 ng) and their combination (4:1) were checked for fall in blood pressure in hypertensive rats (10% fructose in fluid without pretreatment) as well as angiotensin-converting enzyme (ACE) inhibiting activity using guinea pig ileum. An isobolographic analysis was used to characterise the interaction between SACS and CAP for fall in blood pressure and ACE inhibiting evaluations. Administration of captopril, low and high doses of FGH (125, 250 mg/kg), either alone or together showed fall in fluid intake and body weight. The combined therapy of FGH 250 mg/kg and CAP was more effective in reducing systolic blood pressure, cholesterol, triglycerides and glucose. The SOD and catalase activities in heart tissue were significantly elevated in groups treated with FGH, SACS, CAP, FGH+CAP and SACS+CAP. Further, combined therapy of FGH 250 mg/kg and CAP caused significant fall in LDH and CK-MB activities in serum and elevation in heart tissue homogenate. SACS in low dose was less effective than low dose of FGH; similarly, high dose of FGH was more efficacious than high dose of SACS. Corroborating with this, combined therapy of garlic (250 mg/kg) with CAP demonstrated higher synergistic action than combination of SACS (0.222 mg/kg) with CAP suggesting the role of additional bioactive constituents apart from SACS, responsible for therapeutic efficacy of garlic. Moreover, combination of SACS and CAP exerted super-additive (synergistic) interaction wi

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Antioxidants; Blood Glucose; Blood Pressure; Body Weight; Captopril; Creatine Kinase; Cysteine; Drinking; Drug Synergism; Female; Garlic; Guinea Pigs; Heart; Hypertension; Ileum; Isoproterenol; Lipids; Phytotherapy; Plant Extracts; Rats; Rats, Wistar

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.

Topics: Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Blood Urea Nitrogen; Creatinine; Cysteine; Cytoprotection; Garlic; Hypertension; Kidney; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Nephrectomy; Nitric Oxide Synthase Type II; Plant Extracts; Poly Adenosine Diphosphate Ribose; Proteinuria; Rats; Rats, Wistar; Superoxide Dismutase; Systole; Tyrosine

S-Allyl-L-cysteine (SAC), an active organosulfur compound derived from garlic, was found to reduce mortality with lesser incidence of stroke and also to lower the overall stroke-related behavioral score in stroke-prone spontaneously hypertensive (SHRSP) rats by dietary administration. Consequently, the anti-stroke effect of dietary SAC was demonstrated in SHRSP rats.

Topics: Administration, Oral; Animals; Behavior, Animal; Cysteine; Diet; Disease Models, Animal; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Survival Rate