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2019
Khayyal, M. T., M. H. Kreuter, M. Kemmler, P. Altmann, D. H. Abdel-Naby, and M. A. El-Ghazaly, "Effect of a chamomile extract in protecting against radiation-induced intestinal mucositis.", Phytotherapy research : PTR, vol. 33, issue 3, pp. 728-736, 2019.
Khayyal, M. T., F. K. El-Baz, M. R. Meselhy, G. H. Ali, and R. M. El-Hazek, "Intestinal injury can be effectively prevented by in gamma irradiated rats.", Heliyon, vol. 5, issue 5, pp. e01814, 2019. Abstract

is one of the most common microalgae that is used as human food. It is isolated from the salty lakes in El-Fayoum and Lake of Bardawil-Sinai in Egypt and can withstand very high concentrations of salt: The potentiality of , a unicellular biflagellate green alga to protect against intestinal injury induced after radiation exposure was studied. was given orally in doses of 100 and 200 mg/kg to male Wistar rats for 5 days before exposure to 6 Gray (Gy) gamma radiation and continued for a further two days. Rats were sacrificed 24 h later and intestinal segments were dissected out. One segment was examined histologically and another was used to prepare homogenates to assess relevant biochemical parameters reflecting intestinal injury. Radiation exposure led to a rise in the histological damage score, an increase in tissue tumor necrosis factor (TNF-α), interleukin (IL-1β) and thiobarbituric acid reactive substances (TBARS) but a reduction in tissue reduced glutathione (GSH) and in serum citrulline. Pretreatment with either dose of effectively reduced the severity of intestinal mucositis induced by gamma radiation.

Khayyal, M. T., D. H. Abdel-Naby, and M. A. El-Ghazaly, "Propolis extract protects against radiation-induced intestinal mucositis through anti-apoptotic mechanisms.", Environmental science and pollution research international, 2019. Abstract

Intestinal mucositis is a common side effect during radiotherapy that could be largely prevented by compounds possessing anti-inflammatory or anti-oxidant properties, including extracts of propolis containing a high proportion of flavonoids. A specially formulated aqueous extract of propolis (PWE) has been prepared in such a way to preclude the inclusion of flavonoids but contain mostly organic aromatic acids to study whether it would still protect against radiation-induced intestinal mucositis and to study the possible involvement of apoptotic pathways. Rats were exposed to a gamma radiation dose of 8 Gy from a Cesium-137 source in order to inflict intestinal mucositis. Three days before exposure, rats were given PWE orally and treatment continued for 2 more days. Twenty-four hours later, rats were sacrificed, the small intestine was excised, and sections were examined histologically. Different parameters for apoptosis, inflammation, and oxidative stress were determined in the serum and in intestinal homogenates. Radiation exposure led to histological and biochemical signs of intestinal damage. This was associated with an increase in apoptotic indicators and derangement in oxidative stress parameters. All deranged parameters were largely prevented by PWE. The findings provide evidence that the protective effect of PWE against intestinal radiation damage involves not only its anti-inflammatory and anti-oxidant effects but also its anti-apoptotic properties as well.

Khayyal, M. T., W. Wadie, E. A. Abd El-Haleim, K. A. Ahmed, O. Kelber, R. M. Ammar, and H. Abdel-Aziz, "STW 5 is effective against nonsteroidal anti-inflammatory drugs induced gastro-duodenal lesions in rats.", World journal of gastroenterology, vol. 25, issue 39, pp. 5926-5935, 2019. Abstract

BACKGROUND: Proton pump inhibitors are often used to prevent gastro-intestinal lesions induced by nonsteroidal anti-inflammatory drugs. However, they are not always effective against both gastric and duodenal lesions and their use is not devoid of side effects.

AIM: To explore the mechanisms mediating the clinical efficacy of STW 5 in gastro-duodenal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs), exemplified here by diclofenac, in a comparison to omeprazole.

METHODS: Gastro-duodenal lesions were induced in rats by oral administration of diclofenac (5 mg/kg) for 6 successive days. One group was given concurrently STW 5 (5 mL/kg) while another was given omeprazole (20 mg/kg). A day later, animals were sacrificed, stomach and duodenum excised and divided into 2 segments: One for histological examination and one for measuring inflammatory mediators (tumor necrosis factor α, interleukins-1β and 10), oxidative stress enzyme (heme oxygenase-1) and apoptosis regulator (B-cell lymphoma 2).

RESULTS: Diclofenac caused overt histological damage in both tissues, associated with parallel changes in all parameters measured. STW 5 and omeprazole effectively prevented these changes, but STW 5 superseded omeprazole in protecting against histological damage, particularly in the duodenum.

CONCLUSION: The findings support the therapeutic usefulness of STW 5 and its superiority over omeprazole as adjuvant therapy to NSAIDs to protect against their possible gastro-duodenal side effects.

2018
MT, K., E. - H. RM, E. - S. WA, F. J, B. D, and A. - T. M, "Micellar solubilisation enhances the antiinflammatory activities of curcumin and boswellic acids in rats with adjuvant-induced arthritis.", Nutrition, vol. 54, pp. 189-196, 2018.
2015
Abdel-Aziz, H., M. Schneider, W. Neuhuber, A. M. Kassem, S. Khailah, J. Müller, H. G. E. deen, A. Khairy, M. T. Khayyal, A. Shcherbakova, et al., "GPR84 and TREM-1 signaling contribute to the pathogenesis of reflux esophagitis.", Molecular medicine (Cambridge, Mass.), 2015 Nov 24. Abstract

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a non-uniform etiology. Thus the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients.To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced sub-chronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cellline HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein coupled receptor (GPR) 84 in human tissue.Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known pro-inflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was up-regulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly up-regulated in patients with grade B reflux esophagitis.The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

Abdel-Aziz, H., M. Schneider, W. Neuhuber, A. M. Kassem, S. Khailah, J. Müller, H. G. E. deen, A. Khairy, M. T. Khayyal, A. Shcherbakova, et al., "GPR84 and TREM-1 signaling contribute to the pathogenesis of reflux esophagitis.", Molecular medicine (Cambridge, Mass.), 2015 Nov 24. Abstract

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a non-uniform etiology. Thus the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients.To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced sub-chronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cellline HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein coupled receptor (GPR) 84 in human tissue.Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known pro-inflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was up-regulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly up-regulated in patients with grade B reflux esophagitis.The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

Khayyal, M. T., R. M. El-Hazek, and M. A. El-Ghazaly, "Propolis aqueous extract preserves functional integrity of murine intestinal mucosa after exposure to ionizing radiation.", Environmental toxicology and pharmacology, vol. 40, issue 3, pp. 901-6, 2015 Nov. Abstract

The ability of a specially prepared water propolis extract (PWE) to preserve the functional activity of the intestinal mucosa after radiation exposure was studied. PWE was given orally (650mg/kg) to rats five days prior to irradiation by 6Gy and continued for further two days. Rats were sacrificed 24h later, intestinal segments were examined histologically and homogenates were used to assess relevant biochemical parameters reflecting intestinal injury. Irradiation led to a rise in the histological damage score, a rise in tissue TNF-α and TBARS, and a decrease in sucrase, alkaline phosphatase, GSH and cholecystokinin as well as a decrease in plasma citrulline. The findings reflect a decrease in intestinal functional activity. PWE preserved the intestinal integrity and largely protected against the changes induced in the histology damage score and all parameters measured, possibly as a result of the antioxidant and anti-inflammatory action of its caffeic acid content.

Khayyal, M. T., R. M. El-Hazek, and M. A. El-Ghazaly, "Propolis aqueous extract preserves functional integrity of murine intestinal mucosa after exposure to ionizing radiation.", Environmental toxicology and pharmacology, vol. 40, issue 3, pp. 901-6, 2015 Nov. Abstract

The ability of a specially prepared water propolis extract (PWE) to preserve the functional activity of the intestinal mucosa after radiation exposure was studied. PWE was given orally (650mg/kg) to rats five days prior to irradiation by 6Gy and continued for further two days. Rats were sacrificed 24h later, intestinal segments were examined histologically and homogenates were used to assess relevant biochemical parameters reflecting intestinal injury. Irradiation led to a rise in the histological damage score, a rise in tissue TNF-α and TBARS, and a decrease in sucrase, alkaline phosphatase, GSH and cholecystokinin as well as a decrease in plasma citrulline. The findings reflect a decrease in intestinal functional activity. PWE preserved the intestinal integrity and largely protected against the changes induced in the histology damage score and all parameters measured, possibly as a result of the antioxidant and anti-inflammatory action of its caffeic acid content.

Abdel-Aziz, H., W. Wadie, H. F. Zaki, J. Müller, O. Kelber, T. Efferth, and M. T. Khayyal, "Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5.", Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 22, issue 5, pp. 588-95, 2015 May 15. Abstract

BACKGROUND: Many screening procedures for agents with potential usefulness in functional dyspepsia (FD) rely on animals exposed to stress early in life (neonatal maternal separation, NMS) or in adulthood (restraint stress, RS).

PURPOSE: Since many clinical cases of FD have been associated with stress in early life followed by stress in adulthood, a sequential model simulating the clinical situation is described. To explore the validity of the model, the efficacy of STW5, a multicomponent herbal preparation of proven usefulness in FD, was tested.

STUDY DESIGN/METHODS: A sequential stress model established where rats are exposed to NMS after birth followed later by RS in adulthood. Stress hormones and ghrelin were measured in plasma, while responsiveness of stomach fundus strips to smooth muscle stimulants and relaxants was assessed ex-vivo. The effectiveness of treatment with STW5 a few days before and during exposure to RS in preventing changes induced by the stress model is reported and compared to its efficacy when used in animals subjected to RS alone.

RESULTS: Responses to both stimulants and relaxants were reduced to various extents in the studied models, but treatment with STW5 tended to normalize gastric responsiveness. Plasma levels of ghrelin, corticosterone releasing factor, and corticosterone were raised by RS as well as the sequential model. Treatment with STW5 tended to prevent the deranged parameters.

CONCLUSION: The sequential stress model has a place in drug screening for potential usefulness in FD as it simulates more the clinical setting. Furthermore, the findings shed more light on the mechanisms of action of STW5 in FD.

Abdel-Aziz, H., W. Wadie, H. F. Zaki, J. Müller, O. Kelber, T. Efferth, and M. T. Khayyal, "Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5.", Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 22, issue 5, pp. 588-95, 2015 May 15. Abstract

BACKGROUND: Many screening procedures for agents with potential usefulness in functional dyspepsia (FD) rely on animals exposed to stress early in life (neonatal maternal separation, NMS) or in adulthood (restraint stress, RS).

PURPOSE: Since many clinical cases of FD have been associated with stress in early life followed by stress in adulthood, a sequential model simulating the clinical situation is described. To explore the validity of the model, the efficacy of STW5, a multicomponent herbal preparation of proven usefulness in FD, was tested.

STUDY DESIGN/METHODS: A sequential stress model established where rats are exposed to NMS after birth followed later by RS in adulthood. Stress hormones and ghrelin were measured in plasma, while responsiveness of stomach fundus strips to smooth muscle stimulants and relaxants was assessed ex-vivo. The effectiveness of treatment with STW5 a few days before and during exposure to RS in preventing changes induced by the stress model is reported and compared to its efficacy when used in animals subjected to RS alone.

RESULTS: Responses to both stimulants and relaxants were reduced to various extents in the studied models, but treatment with STW5 tended to normalize gastric responsiveness. Plasma levels of ghrelin, corticosterone releasing factor, and corticosterone were raised by RS as well as the sequential model. Treatment with STW5 tended to prevent the deranged parameters.

CONCLUSION: The sequential stress model has a place in drug screening for potential usefulness in FD as it simulates more the clinical setting. Furthermore, the findings shed more light on the mechanisms of action of STW5 in FD.

Abdel-Aziz, H., W. Wadie, O. Scherner, T. Efferth, and M. T. Khayyal, "Bacteria-Derived Compatible Solutes Ectoine and 5α-Hydroxyectoine Act as Intestinal Barrier Stabilizers to Ameliorate Experimental Inflammatory Bowel Disease.", Journal of natural products, vol. 78, issue 6, pp. 1309-15, 2015 Jun 26. Abstract

Earlier studies showed that the compatible solute ectoine (1) given prophylactically before induction of colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats prevented histological changes induced in the colon and the associated rise in inflammatory mediators. This study was therefore conducted to investigate whether ectoine (1) and its 5α-hydroxy derivative (2) would also be effective in treating an already established condition. Two days after inducing colitis in rats by instilling TNBS/alcohol in the colon, animals were treated orally once daily for 1 week with either 1 or 2 (50, 100, 300 mg/kg). Twenty-four hours after the last drug administration rats were sacrificed. Ulcerative lesions and colon mass indices were reduced by 1 and 2 in a bell-shaped manner. Best results were obtained with 100 mg/kg ectoine (1) and 50 mg/kg 5α-hydroxyectoine (2). The solutes normalized the rise in myeloperoxidase, TNFα, and IL-1β induced by TNBS but did not affect levels of reduced glutathione or ICAM-1, while reducing the level of fecal calprotectin, an established marker for inflammatory bowel disease. The findings indicate that the naturally occurring compatible solutes ectoine (1) and 5α-hydroxyectoine (2) possess an optimum concentration that affords maximal intestinal barrier stabilization and could therefore prove useful for better management of human inflammatory bowel disease.

Abdel-Aziz, H., W. Wadie, O. Scherner, T. Efferth, and M. T. Khayyal, "Bacteria-Derived Compatible Solutes Ectoine and 5α-Hydroxyectoine Act as Intestinal Barrier Stabilizers to Ameliorate Experimental Inflammatory Bowel Disease.", Journal of natural products, vol. 78, issue 6, pp. 1309-15, 2015 Jun 26. Abstract

Earlier studies showed that the compatible solute ectoine (1) given prophylactically before induction of colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats prevented histological changes induced in the colon and the associated rise in inflammatory mediators. This study was therefore conducted to investigate whether ectoine (1) and its 5α-hydroxy derivative (2) would also be effective in treating an already established condition. Two days after inducing colitis in rats by instilling TNBS/alcohol in the colon, animals were treated orally once daily for 1 week with either 1 or 2 (50, 100, 300 mg/kg). Twenty-four hours after the last drug administration rats were sacrificed. Ulcerative lesions and colon mass indices were reduced by 1 and 2 in a bell-shaped manner. Best results were obtained with 100 mg/kg ectoine (1) and 50 mg/kg 5α-hydroxyectoine (2). The solutes normalized the rise in myeloperoxidase, TNFα, and IL-1β induced by TNBS but did not affect levels of reduced glutathione or ICAM-1, while reducing the level of fecal calprotectin, an established marker for inflammatory bowel disease. The findings indicate that the naturally occurring compatible solutes ectoine (1) and 5α-hydroxyectoine (2) possess an optimum concentration that affords maximal intestinal barrier stabilization and could therefore prove useful for better management of human inflammatory bowel disease.

El-Ghazaly, M. A., R. M. El-Hazek, and M. T. Khayyal, "Protective effect of the herbal preparation, STW 5, against intestinal damage induced by gamma radiation in rats.", International journal of radiation biology, vol. 91, issue 2, pp. 150-6, 2015 Feb. Abstract

PURPOSE: STW 5 (marketed as Iberogast(®), Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory properties and antioxidant activity. We investigated the effect of STW 5 against intestinal injury induced after whole body exposure to ionizing radiation (IR).

MATERIALS AND METHODS: Intestinal mucositis was induced in rats by irradiation at a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were tested to assess biochemical parameters indicating intestinal injury and jejunum segments were exposed to semi-quantitative histological examination.

RESULTS: IR led to an increase in overall damage severity (ODS) score associated with a significant rise in tumor necrosis factor (TNF-α) and thiobarbituric acid reactive substances (TBARS) by 46% and 50% (p ≤ 0.05), respectively, whereas the reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities were significantly decreased by 68%, 76% and 25% (p ≤ 0.05), respectively, in intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment with STW 5 guarded against the changes in ODS score and in all parameters measured.

CONCLUSION: Pre-treatment with STW 5 has the potential to decrease the severity of radiation-induced mucositis.

El-Ghazaly, M. A., R. M. El-Hazek, and M. T. Khayyal, "Protective effect of the herbal preparation, STW 5, against intestinal damage induced by gamma radiation in rats.", International journal of radiation biology, vol. 91, issue 2, pp. 150-6, 2015 Feb. Abstract

PURPOSE: STW 5 (marketed as Iberogast(®), Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory properties and antioxidant activity. We investigated the effect of STW 5 against intestinal injury induced after whole body exposure to ionizing radiation (IR).

MATERIALS AND METHODS: Intestinal mucositis was induced in rats by irradiation at a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were tested to assess biochemical parameters indicating intestinal injury and jejunum segments were exposed to semi-quantitative histological examination.

RESULTS: IR led to an increase in overall damage severity (ODS) score associated with a significant rise in tumor necrosis factor (TNF-α) and thiobarbituric acid reactive substances (TBARS) by 46% and 50% (p ≤ 0.05), respectively, whereas the reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities were significantly decreased by 68%, 76% and 25% (p ≤ 0.05), respectively, in intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment with STW 5 guarded against the changes in ODS score and in all parameters measured.

CONCLUSION: Pre-treatment with STW 5 has the potential to decrease the severity of radiation-induced mucositis.

Khayyal, M. T., A. M. Agha, H. F. Zaki, A. El-Sahar, and H. Abdel-Aziz, "Mechanisms Involved in the Anti-inflammatory and Vascular Effects of Iberis amara Extract.", Planta medica, vol. 81, issue 12-13, pp. 1097-102, 2015 Aug. Abstract

The anti-inflammatory potential and vasoprotective effects of an Iberis amara extract in a rat model of arthritis were investigated. I. amara, or bitter candytuft, has long been known for its anti-inflammatory properties on account of its active constituents, including cucurbitacins, kaempferol, and sinapic acid. The present study was intended to explore more in depth its anti-inflammatory activity in both acute (carrageenan rat paw edema) and chronic (adjuvant-induced arthritis) models of inflammation. An extract of I. amara dose-dependently reduced the extent of edema in both models. In the chronic model, this was associated with a reduction in the inflammation mediators tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 and in the antioxidant biomarkers malondialdehyde and total nitrate/nitrite. Because arthritis was reported both clinically and experimentally to contribute towards different vascular complications, it was of interest to study ex vivo the sensitivity of aortic rings in our experimental setup towards norepinephrine, acetylcholine, and sodium nitroprusside. The aortic rings from arthritic rats showed no change in sensitivity to norepinephrine, but showed a reduced sensitivity to sodium nitroprusside and acetylcholine. To show whether the treatment of the arthritis would restore endothelial function, I. amara extract was shown to markedly reduce the reactivity to norepinephrine, but not to appreciably affect the reactivity towards sodium nitroprusside and it had a tendency towards normalizing reactivity to acetylcholine. Taken collectively, the findings imply an improvement in endothelial function and lend support to the use of the extract in rheumatic inflammatory conditions to help safeguard the integrity of the endothelium and reduce the risk of vascular complications.

Khayyal, M. T., A. M. Agha, H. F. Zaki, A. El-Sahar, and H. Abdel-Aziz, "Mechanisms Involved in the Anti-inflammatory and Vascular Effects of Iberis amara Extract.", Planta medica, vol. 81, issue 12-13, pp. 1097-102, 2015 Aug. Abstract

The anti-inflammatory potential and vasoprotective effects of an Iberis amara extract in a rat model of arthritis were investigated. I. amara, or bitter candytuft, has long been known for its anti-inflammatory properties on account of its active constituents, including cucurbitacins, kaempferol, and sinapic acid. The present study was intended to explore more in depth its anti-inflammatory activity in both acute (carrageenan rat paw edema) and chronic (adjuvant-induced arthritis) models of inflammation. An extract of I. amara dose-dependently reduced the extent of edema in both models. In the chronic model, this was associated with a reduction in the inflammation mediators tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 and in the antioxidant biomarkers malondialdehyde and total nitrate/nitrite. Because arthritis was reported both clinically and experimentally to contribute towards different vascular complications, it was of interest to study ex vivo the sensitivity of aortic rings in our experimental setup towards norepinephrine, acetylcholine, and sodium nitroprusside. The aortic rings from arthritic rats showed no change in sensitivity to norepinephrine, but showed a reduced sensitivity to sodium nitroprusside and acetylcholine. To show whether the treatment of the arthritis would restore endothelial function, I. amara extract was shown to markedly reduce the reactivity to norepinephrine, but not to appreciably affect the reactivity towards sodium nitroprusside and it had a tendency towards normalizing reactivity to acetylcholine. Taken collectively, the findings imply an improvement in endothelial function and lend support to the use of the extract in rheumatic inflammatory conditions to help safeguard the integrity of the endothelium and reduce the risk of vascular complications.

Hagl, S., R. Grewal, I. Ciobanu, A. Helal, M. T. Khayyal, W. E. Muller, and G. P. Eckert, "Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease.", Journal of Alzheimer's disease : JAD, vol. 43, issue 3, pp. 927-38, 2015. Abstract

Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD.

Hagl, S., R. Grewal, I. Ciobanu, A. Helal, M. T. Khayyal, W. E. Muller, and G. P. Eckert, "Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease.", Journal of Alzheimer's disease : JAD, vol. 43, issue 3, pp. 927-38, 2015. Abstract

Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD.

Hagl, S., R. Grewal, I. Ciobanu, A. Helal, M. T. Khayyal, W. E. Muller, and G. P. Eckert, "Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease.", Journal of Alzheimer's disease : JAD, vol. 43, issue 3, pp. 927-38, 2015. Abstract

Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD.

2014
Khayyal, M. T., D. H. Abdel-Naby, H. Abdel-Aziz, and M. A. El-Ghazaly, "A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.", Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 21, issue 11, pp. 1390-9, 2014 Sep 25. Abstract

PURPOSE: Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect.

METHODS: Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress.

RESULTS: Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters.

CONCLUSION: The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers.

Khayyal, M. T., D. H. Abdel-Naby, H. Abdel-Aziz, and M. A. El-Ghazaly, "A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.", Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 21, issue 11, pp. 1390-9, 2014 Sep 25. Abstract

PURPOSE: Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect.

METHODS: Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress.

RESULTS: Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters.

CONCLUSION: The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers.

Khayyal, M. T., D. H. Abdel-Naby, H. Abdel-Aziz, and M. A. El-Ghazaly, "A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.", Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 21, issue 11, pp. 1390-9, 2014 Sep 25. Abstract

PURPOSE: Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect.

METHODS: Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress.

RESULTS: Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters.

CONCLUSION: The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers.

2013
Hagl, S., A. Kocher, C. Schiborr, S. H. Eckert, I. Ciobanu, M. Birringer, H. El-Askary, A. Helal, M. T. Khayyal, J. Frank, et al., "Rice bran extract protects from mitochondrial dysfunction in guinea pig brains.", Pharmacological research, vol. 76, pp. 17-27, 2013 Oct. Abstract

Mitochondrial dysfunction plays a major role in the development of age-related neurodegenerative diseases and recent evidence suggests that food ingredients can improve mitochondrial function. In the current study we investigated the effects of feeding a stabilized rice bran extract (RBE) on mitochondrial function in the brain of guinea pigs. Key components of the rice bran are oryzanols, tocopherols and tocotrienols, which are supposed to have beneficial effects on mitochondrial function. Concentrations of α-tocotrienol and γ-carboxyethyl hydroxychroman (CEHC) but not γ-tocotrienol were significantly elevated in brains of RBE fed animals and thus may have provided protective properties. Overall respiration and mitochondrial coupling were significantly enhanced in isolated mitochondria, which suggests improved mitochondrial function in brains of RBE fed animals. Cells isolated from brains of RBE fed animals showed significantly higher mitochondrial membrane potential and ATP levels after sodium nitroprusside (SNP) challenge indicating resistance against mitochondrial dysfunction. Experimental evidence indicated increased mitochondrial mass in guinea pig brains, e.g. enhanced citrate synthase activity, increased cardiolipin as well as respiratory chain complex I and II and TIMM levels. In addition levels of Drp1 and fis1 were also increased in brains of guinea pigs fed RBE, indicating enhanced fission events. Thus, RBE represents a potential nutraceutical for the prevention of mitochondrial dysfunction and oxidative stress in brain aging and neurodegenerative diseases.

Hagl, S., A. Kocher, C. Schiborr, S. H. Eckert, I. Ciobanu, M. Birringer, H. El-Askary, A. Helal, M. T. Khayyal, J. Frank, et al., "Rice bran extract protects from mitochondrial dysfunction in guinea pig brains.", Pharmacological research, vol. 76, pp. 17-27, 2013 Oct. Abstract

Mitochondrial dysfunction plays a major role in the development of age-related neurodegenerative diseases and recent evidence suggests that food ingredients can improve mitochondrial function. In the current study we investigated the effects of feeding a stabilized rice bran extract (RBE) on mitochondrial function in the brain of guinea pigs. Key components of the rice bran are oryzanols, tocopherols and tocotrienols, which are supposed to have beneficial effects on mitochondrial function. Concentrations of α-tocotrienol and γ-carboxyethyl hydroxychroman (CEHC) but not γ-tocotrienol were significantly elevated in brains of RBE fed animals and thus may have provided protective properties. Overall respiration and mitochondrial coupling were significantly enhanced in isolated mitochondria, which suggests improved mitochondrial function in brains of RBE fed animals. Cells isolated from brains of RBE fed animals showed significantly higher mitochondrial membrane potential and ATP levels after sodium nitroprusside (SNP) challenge indicating resistance against mitochondrial dysfunction. Experimental evidence indicated increased mitochondrial mass in guinea pig brains, e.g. enhanced citrate synthase activity, increased cardiolipin as well as respiratory chain complex I and II and TIMM levels. In addition levels of Drp1 and fis1 were also increased in brains of guinea pigs fed RBE, indicating enhanced fission events. Thus, RBE represents a potential nutraceutical for the prevention of mitochondrial dysfunction and oxidative stress in brain aging and neurodegenerative diseases.