Immunomodulatory effects of cadmium and Gynostemma pentaphyllum herbal tea on rat splenocyte proliferation.

Gynostemma pentaphyllum Makino (GP) is a herbal tea widely grown in Southeast Asia. However, this herbal tea can be contaminated with some heavy metals, especially cadmium (Cd), from agricultural areas, which may affect human health. The objective of this study is to evaluate the immunomodulatory effects of Cd contaminated in GP herbal tea and inorganic Cd on rat splenocytes. Rats were divided into groups and treated with drinking water (control), high CdCl 2 in drinking water (HCd; 0.05 mg/L), GP herbal tea containing 0.05 mg/L Cd (GP-HCd) for 4 months, low CdCl 2 in drinking water (LCd; 0.006 mg/L), and GP herbal tea containing 0.006 mg/L Cd (GP-LCd) for 6 months. After the treatments, Cd accumulation in organs and blood was detected by using a graphite furnace atomic absorption spectrophotometer. In spleen, HCd-treated rats had 4-fold higher Cd accumulations than GP-HCd-treated rats. Cd accumulation in liver and kidney in the HCd group also increased significantly. There were no significant changes in total leucocyte and lymphocyte counts; however, these parameters tended to decrease slightly in LCd, GP-LCd, and GP-HCd groups. The HCd group (ex vivo) significantly produced suppressive effects on T cell mitogen-induced splenocyte proliferation, with 1 mug/mL Con A and PHA-P. In addition, 0.5 mug/mL PWM-induced B cell proliferation, through T cell functions, was also significantly inhibited by HCd as compared to the control group, while GP-HCd had no effects. However, both GP-LCd- and LCd-treated rats had a slight increase in Con A-stimulated splenocyte proliferation. This study indicated that high Cd contamination in drinking water alone had suppressive effects on T cell functions, but these effects could not be found with the same Cd level contamination in GP herbal tea.

Attenuation of eNOS expression in cadmium-induced hypertensive rats.

Cadmium (Cd) has been reported to induce hypertension in both humans and animals; however, its mechanism has not been clearly elucidated. Vascular tone is one of the factors contributing to hypertension. This study was conducted to investigate the effects of Cd exposure on vascular muscarinic receptor responses to acetylcholine (ACh) in isolated aortas. Male Sprague-Dawley rats were exposed to Cd via drinking water (5, 10 and 50 ppm) for 3 months. Cd 10 and 50 ppm exposure caused significant decreases in the sensitivity of vascular muscarinic receptors to ACh. However, Cd exposure did not alter the vascular relaxation induced by sodium nitroprusside (SNP) which is a nitric oxide donor. Consistent with the reduction of ACh-induced relaxation, treatment with Cd decreased endothelial nitric oxide synthase (eNOS) protein level in blood vessels. These results suggested that Cd suppressed ACh-induced vascular relaxation by interfering with muscarinic receptor function, and its downstream signaling pathway may be one of the contributing factors for the development of hypertension.

Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts.

Andrographis paniculata has been widely used as a traditional medicine for the treatment of common cold, diarrhea and hypertension. The three major active diterpenoids are andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4). It has been reported that AP3 has hypotensive and vasorelaxation effects. However, there is only limited information on the cardiovascular effects of the other diterpenoids and crude extracts containing different levels of AP3. Therefore, the present study investigated the effects of these diterpenoids, AP1, AP3, and AP4, isolated from A. paniculata, and different aqueous plant extracts on blood pressure, vascular and chronotropic responses by using conscious rats and their isolated aortas and right atria as the test models. Among the three major diterpenoids, AP3 was the most potent compound for inducing vasorelaxation and decreasing heart rate. In addition, Extract B (high level of AP3) had greater hypotensive effect in conscious rats than Extract A (low level of AP3). Verapamil, a Ca2+ channel blocker, also had a hypotensive effect less than that of Extract C containing a high level of AP3. At the doses and durations of Extract A and B which produced hypotension, the responses of the Extract A-treated aorta to norepinephrine, and the vascular muscarinic responses to acetylcholine of both extracts were decreased. However, repeated doses of both extracts did not alter cardiac beta-adrenoceptor and muscarinic responses of extract-treated rats to NE and ACh, respectively. The results of this study suggest that vascular smooth muscle is the major site of these hypotensive effects of both AP3 and A. paniculata extracts. Furthermore, the consumption of A. paniculata products containing high levels of AP3 may be responsible for causing hypotension in some patients taking this herbal drug.