Laxative effects and mechanism of action of Brazilian green propolis.

BACKGROUND: Brazilian green propolis is reported to have wide range of biological properties including antibacterial, anti-inflammatory, anti-influenza, and antioxidant activities. In the digestive system, a protective effect of propolis on gastric ulcer has been reported, but a laxative effect has not yet been reported. We investigated the effect and the mechanism of action of water and ethanol extracts of Brazilian green propolis. METHODS: We examined the laxative effect of propolis on stool frequency by administering orally an ethanol extract of propolis (EEP) or a water extract of propolis (WEP) at 10, 50, 100, or 500 mg/kg to normal mice. We then investigated the effects of propolis using constipation model mice induced by two types of drugs, loperamide (a µ opioid receptor agonist) and clonidine (an α-2 adrenergic receptor agonist). We also investigated the effects of WEP on gastrointestinal transit and contractional tension of the ileum to uncover the mechanism of action of WEP. RESULTS: Treatment with WEP, but not with EEP, significantly increased the weight of stools (p<0.01 at 500 mg/kg). WEP treatment significantly restored stool frequency and stool weight in clonidine-induced constipation model mice, but not in loperamide-induced constipation model mice. WEP treatment did not affect gastro-intestinal transit, but significantly increased the contractional tension of the isolated ileum of guinea pigs. This increase was inhibited by an acetylcholine receptor antagonist (atropine), but not by a 5-HT receptor antagonist (GR113808). CONCLUSION: These findings indicate that WEP has laxative effects both in normal mice and in clonidine-induced constipation model mice. The laxative effects of WEP might be mediated by increased contractional tension of the ileum exerted at least in part via activation of an acetylcholine receptor.

Agarwood induced laxative effects via acetylcholine receptors on loperamide-induced constipation in mice.

Agarwood (Aquilaria sinensis, Aquilaria crasna) is well known as an incense in the oriental region such as Thailand, Taiwan, and Cambodia, and is used as a digestive in traditional medicine. We investigated the laxative effects and mechanism of agarwood leaves extracted with ethanol (EEA-1, Aquilaria sinensis; EEA-2, Aquilaria crasna). EEA-1, EEA-2, the main constituents of EEAs (mangiferin, and genkwanin-5-O-primeveroside), and senna increased the frequency and weight of stools in loperamide-induced constipation model mice. EEA-1 and EEA-2 did not induce diarrhea as a side effect, but senna induced severe diarrhea. EEA-1 and senna increased gastro-intestinal (GI) transit in the model mice. EEA-1, but not senna, also increased the intestinal tension of isolated jejunum and ileum in guinea pigs, and the tension increase was blocked by atropine, a muscarinic receptor antagonist, but not by other inhibitors (granicetron, pyrilamine, or bradykinin-antagonist peptide). Furthermore, the increase in frequency and weight of stools induced by EEA-1 were blocked by pre-administration of atropine in the model mice. These findings indicate that EEAs exerted a laxative effect via acetylcholine receptors in the mouse constipation model.

1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of bee products and their constituents determined by ESR.

The aim of this work was to investigate the antioxidant property of honeybee products and their constituents using an ESR method. Antioxidative activity was evaluated as the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The DPPH radical scavenging activities, in descending order, were: ethanol extract of Chinese red propolis>ethanol extract of Brazilian green propolis>water extract of Brazilian green propolis>ethanol extract of bee pollen. Many natural compounds are included in Brazilian green propolis, such as caffeoylquinic acid derivatives [3,4-di-caffeoylquinic acid (3,4-CQA), 3,5-di-caffeoylquinic acid (3,5-CQA), and chlorogenic acid (ChA)] and cinnamic acid derivatives [artepillin C, baccharin, rho-coumaric acid, and drupanin]. Caffeoylquinic acid derivatives exhibited DPPH radical scavenging activity as strong as that of ascorbic acid and trolox. Among the cinnamic acid derivatives, artepillin C exhibited relatively strong DPPH radical scavenging activity. Caffeic acid phenethyl ester (CAPE), a constituent of Chinese red propolis, exhibited potent DPPH radical scavenging activity, stronger than that of ascorbic acid and trolox. Caffeic acid, a metabolite of caffeoylquinic acid, exhibited powerful DPPH radical scavenging activity, while quinic acid, another metabolite of caffeoylquinic acid, had no such activity. Both Brazilian and Chinese propolis and their constituents (caffeoylquinic acid derivatives and CAPE) therefore appear to be powerful scavengers of DPPH radical, and the effects may be partly dependent on the nature of their caffeoyl groups.

Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs). METHODS: In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE. RESULTS: RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation. CONCLUSION: Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.

10-Hydroxy-2-decenoic acid, a major fatty acid from royal jelly, inhibits VEGF-induced angiogenesis in human umbilical vein endothelial cells.

Vascular endothelial growth factor (VEGF) is reported to be a potent pro-angiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. Royal jelly (RJ) is a honeybee product containing various proteins, sugars, lipids, vitamins and free amino acids. 10-Hydroxy-2-decenoic acid (10HDA), a major fatty acid component of RJ, is known to have various pharmacological effects; its antitumor activity being especially noteworthy. However, the mechanism underlying this effect is unclear. We examined the effect of 10HDA on VEGF-induced proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Our findings showed that, 10HDA at 20 microM or more significantly inhibited such proliferation, migration and tube formation. Similarly, 10 microM GM6001, a matrix metalloprotease inhibitor, prevented VEGF-induced migration and tube formation. These findings indicate that 10HDA exerts an inhibitory effect on VEGF-induced angiogenesis, partly by inhibiting both cell proliferation and migration. Further experiments will be needed to clarify the detailed mechanism.