Mona A. EI-Ghazalyl, Rasha R. A. Rashed 1 & Mohamed T. Khayyal 2

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Department of Drug Radiation Research, National Centre for Radiation Research and Technology, Atomic Energy Authority, Egypt, and 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, Egypt.

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Abstract

Purpose: To study the effect of aqueous propolis extract (AEP) against indomethacin {lndo)-induced gastric ulcers in irradiated and non-irradiated rats. Materials and methods: Animals were irradiated at different radiation dose levels before the induction of ulcers. AEP was injected orally 1 hour before induction of gastric ulcers and the effects compared with those of lansoprazole (lanso), which was used as a reference anti-ulcerogenic drug. Results: Pretreatment of rats, either irradiated or non-irradiated, with AEP effectively protected against Indo-induced gastric ulceration. This was associated with a reduction in acid output and peptic activity and an increase in the secretion of mucin. The mucosal prostaglandin E2 (PGE2) level was also increased. The levels of tumor necrosis factor-alpha (TNF-a) and interleukin-l beta (ll-l P) were suppressed to the same extent after treatment. Both propolis and lanso were effective in reducing the number of gastric lesions as well as the plasma level of malondialdehyde (MDA). Conclusions: These findings indicate that the gastroprotective effect of AEP could be of value in the management of excessive gastric damage induced by radiation exposure.

M. T. Khayyala*, M. A. El-Ghazalyb, A. S. El-Khatiba , A. M. Hatemc, P. J. F. de Vriesd, S. El-Shafeic, M. M. Khattaba

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Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Department of Drug Radiation Research, National Center for Radiation Research and Technology, Cairo, Egypt cDepartment of Chest Diseases, Faculty of Medicine, Cairo University, Cairo, Egypt.
Friesland-Coberco Dairy Foods, Corporate Research, Deventer, the Netherlands.

Abstract

The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of > 15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2–5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19–52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improve- ment of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19% increase in FVC, a 29.5% increase in FEV1, a 30% increase in peak expiratory flow rate (PEFR), and a 41% increase in the forced expiratory flow rate between 25 and 75% of the vital capacity (FEF25-75). The clinical improvement was associated with decreases by 52, 65, 44 and 30%, respectively, of initial values for the pro-inflammatory cytokines tumor necrosis factor (TNF)-a, ICAM-1, interleukin (IL)-6 and IL-8, and a 3-fold increase in the ‘protective’ cytokine IL-10. The levels of prostaglandins E2 and F2a and leukotriene D4 were decreased significantly to 36, 39, and 28%, respectively, of initial values. Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators. The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients. The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents.

Takemura T, Urushisaki T, Fukuoka M, Hosokawa-Muto J, Hata T, Okuda Y, Hori S, Tazawa S, Araki Y, Kuwata K.

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Nagaragawa Research Center, API Co., Ltd., 692-3 Nagara, Gifu 502-0071, Japan.

Abstract

Brazilian green propolis water extract (PWE) and its chemical components, caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA), act against the influenza A virus (IAV) without influencing the viral components. Here, we evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE (Brazilian green propolis ethanol extract) at a dose of 200 mg/kg was orally administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33. The lifetimes of the PWE-treated mice were significantly extended compared to the untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE, at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased. These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.

Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury models.
Basnet P, Matsushige K, Hase K, Kadota S, Namba T.
Source

Research Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medical and Pharmaceutical University, Japan.
Abstract

The water extract of propolis (PWE) showed a strong hepatoprotective activity against CCl4-toxicity in rats and D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. The PWE also showed a significant hepatoprotective activity against CCl4-induced liver cell injury in cultured rat hepatocytes. The in vitro hepatoprotective activity guided fractionation and chemical analysis led to the isolation of four dicaffeoyl quinic acid derivatives from the PWE. The structure of these isolates was determined to be methyl 3,4-di-O-caffeoyl quinate (1), 3,4-di-O-caffeoyl quinic acid (2), methyl 4,5-di-O-caffeoyl quinate (3), and 3,5-di-O-caffeoyl quinic acid (4) by spectroscopic methods. These compounds were more potent hepatoprotective agents than glycyrrhizin at a concentration of 10 micrograms/ml and 1 was the most potent among the four compounds in the cultured hepatocytes. Quinic acid (5) alone did not show hepatoprotective effects in cultured rat hepatocytes against CCl4-toxicity. On the other hand, chlorogenic acid (6) or caffeic acid alone was found to be less potent than the dicaffeoyl quinic acid derivatives.

Urushisaki T, Takemura T, Tazawa S, Fukuoka M, Hosokawa-Muto J, Araki Y, Kuwata K.

Source

Nagaragawa Research Center, API Co., Ltd., 692-3 Nagara, Yamasaki, Gifu 502-0071, Japan.

Abstract

Influenza A viral infections reached pandemic levels in 1918, 1957, 1968, and, most recently, in 2009 with the emergence of the swine-origin H1N1 influenza virus. The development of novel therapeutics or prophylactics for influenza virus infection is urgently needed. We examined the evaluation of the anti-influenza virus (A/WSN/33 (H1N1)) activity of Brazilian green propolis water extract (PWE) and its constituents by cell viability and real-time PCR assays. Our findings showed strong evidence that PWE has an anti-influenza effect and demonstrate that caffeoylquinic acids are the active anti-influenza components of PWE. Furthermore, we have found that the amount of viral RNA per cell remained unchanged even in the presence of PWE, suggesting that PWE has no direct impact on the influenza virus but may have a cytoprotective activity by affecting internal cellular process. These findings indicate that caffeoylquinic acids are the active anti-influenza components of PWE. Above findings might facilitate the prophylactic application of natural products and the realization of novel anti-influenza drugs based on caffeoylquinic acids, as well as further the understanding of cytoprotective intracellular mechanisms in influenza virus-infected cells.