No abstract

Taurine (T) was first noted as beneficial for stroke and cardiovascular diseases (CVD) prevention in genetic rat models, stroke-prone spontaneously hypertensive rats (SHRSP). The preventive mechanisms of T were ascribed to sympathetic modulation for reducing blood pressure (BP) and anti-inflammatory action. Recent epidemiological surveys revealed the involvement of inflammatory mediators in the pathogenesis of stroke and also atherosclerosis for which T was proven to be effective experimentally. Arterio-lipidosis prone rats, a substrain of SHRSP selectively bred for higher reactive hypercholesterolemia, quickly develop not only arterial fat deposition but also fatty liver which could be attenuated by dietary T supplementation. CARDIAC (CVD and Alimentary Comparison) Study was a WHO-coordinated multi-center epidemiological survey on diets and CVD risks and mortalities in 61 populations. Twenty-four-hour urinary (24U) T was inversely related significantly with coronary heart disease mortality. Higher 24U-T excreters had significantly lower body mass index, systolic and diastolic BP, total cholesterol (T-Cho), and atherogenic index (AI: T-Cho/high density lipoprotein-cholesterol) than lower T excreters. T effects on CVD risks were intensified in individuals whose 24U-T and -magnesium (M) excretions were higher. Furthermore, higher Na excreters with higher heart rate whose BP were significantly higher than those with lower heart rate were divided into two groups by the mean of 24U-T, high and low T excreters. Since the former showed significantly lower BP than the latter, T may beneficially affect salt-sensitive BP rise. Included among the typical 61 populations, were Guiyang, China or St. John’s, Newfoundland, Canada where in which the means of both 24U-T and -M were high or low, respectively. The former and the latter had low and high CVD risks, respectively. Australian Aboriginals living at the coastal area in Victoria were supposed to eat T- and M-rich bush and sea foods and be free from CVD 200 years ago, but they presently have nearly the highest CVD risks indicating that T- and/or M-containing seafood, vegetables, fruits, nuts, milk, etc, similar to prehistoric hunters’ and gatherers’ food should be good for CVD prevention. The preventive effects of T, good for health and longevity, first noted experimentally, were also proven epidemiologically in humans.

Propolis possesses various physiological activities. In this study, we examined the antiangiogenic and antioxidant activities of various components from propolis: acacetin, apigenin, artepillin C, caffeic acid phenethyl ester, chrysin, p-coumaric acid, galangin, kaempferol, pinocembrin, and quercetin. The effects of these components were tested on in vitro models of angiogenesis, tube formation and growth of human umbilical vein endothelial cells (HUVECs). Furthermore, these components were evaluated for their antioxidant activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging and ferric reducing/antioxidant power (FRAP) assays. Two propolis components, caffeic acid phenethyl ester, and quercetin, possessed strong inhibitory effects on tube formation and on endothelial cell proliferation and, coincidentally, showed strong antioxidant activity. Artepillin C, galangin, and kaempferol also possessed strong antiangiogenic and antioxidant activities to a slightly less degree. In contrast, acacetin, apigenin, and pinocembrin possessed a considerable degree of antiangiogenic activities, although they showed very low antioxidant activities. From these results, we propose that components from propolis such as artepillin C, caffeic acid phenethyl ester, galangin, kaempferol, and quercetin might represent a new class of dietary-derived antioxidative compounds with antiangiogenic activities. These propolis components may have the potential to be developed into pharmaceutical drugs for the treatment of angiogenesis-dependent human diseases such as tumors.

There are mainly three types of propolis whose major anticancer ingredients are entirely different: (1) CAPE (caffeic acid phenethyl ester)-based propolis in Europe, Far East and New Zealand, (2) artepillin C (ARC)-based Brazilian green propolis and (3) Brazilian red propolis. It was shown previously that NF (neurofibromatosis)-associated tumors require the kinase PAK1 for their growth, and CAPE-based propolis extracts such as Bio 30 suppress completely the growth of NF tumors in vivo by blocking PAK1 signaling. Also it was demonstrated that ARC suppresses angiogenesis, suggesting the possibility that ARC also blocks oncogenic PAK1 signaling. Here it is shown for the first time that both ARC and green propolis extract (GPE) indeed block the PAK1 signaling selectively, without affecting another kinase known as AKT. Furthermore, it was confirmed that ARC as well as GPE suppress almost completely the growth of human NF tumor xenografts in mice, as does Bio 30. These results suggest that both CAPE-based and ARC-based propolis extracts are natural anti-PAK1 remedies and could be among the first effective NF therapeutics available on the market. Since more than 70% of human cancers such as breast and prostate cancers require the kinase PAK1 for their growth, it is quite possible that GPE could be potentially useful for the treatment of these cancers, as is Bio 30.

Melinjo (Gnetum gnemon L.) seed extract (MSE) and its active ingredient gnetin C (GC), a resveratrol dimer, have been shown to possess a broad spectrum of pharmacological activities. In this study, we investigated the antitumor activity of MSE and GC using human and murine tumor cell culture models in vitro. The antitumor activity of GC was compared with trans-resveratrol (tRV), a stilbenoid polyphenol. Our results show that MSE and GC at clinically achievable concentrations significantly inhibited the proliferation of pancreatic, prostate, breast, and colon cancer cell types (P < 0.05), without affecting normal cells. Interestingly, GC exerts enhanced antitumor activity than that of tRV (P < 0.05). MSE and GC significantly induced apoptosis in all the cancer cells, indicating MSE and GC inhibit tumor cell growth by inducing apoptosis (P < 0.001). Our findings provide evidence that MSE might induce apoptosis in cancer cells via caspase-3/7-dependent and -independent mechanisms. However, GC might trigger both early and late stage apoptosis in cancer cells, at least in part by activating caspase 3/7-dependent mechanisms. Furthermore, the antitumor efficacy of MSE observed in vitro was also validated in a widely used colon-26 tumor-bearing mouse model. Oral administration of MSE at 50 and 100 mg/kg per day significantly inhibited tumor growth, intratumoral angiogenesis, and liver metastases in BALB/c mice bearing colon-26 tumors (P < 0.05). In conclusion, our findings provide evidence that MSE and GC have potent antitumor activity. Most importantly, we provide the first evidence that MSE inhibits tumor growth, intratumoral angiogenesis, and liver metastasis in a colon-26 tumor-bearing mice.