Extract from Aronia melanocarpa, Lonicera caerulea, and Vaccinium myrtillus Improves near Visual Acuity in People with Presbyopia.

Presbyopia is a global problem with an estimated 1.3 billion patients worldwide. In the area of functional food applications, dietary supplements or herbs, there are very few reports describing the positive effects of their use. In the available literature, there is a lack of studies in humans as well as on an animal model of extracts containing, simultaneously, compounds from the polyphenol group (in particular, anthocyanins) and iridoids, so we undertook a study of the effects of a preparation composed of these compounds on a condition of the organ of vision. Our previous experience on a rabbit model proved the positive effect of taking an oral extract of Cornus mas in stabilizing the intraocular pressure of the eye. The purpose of this study was to evaluate the effect of an orally administered ternary compound preparation on the status of physiological parameters of the ocular organ. The preparation contained an extract of the chokeberry Aronia melanocarpa, the honeysuckle berry Lonicera caerulea L., and the bilberry Vaccinium myrtillus (hereafter AKB) standardized for anthocyanins and iridoids, as bioactive compounds known from the literature. A randomized, double-blind, cross-over study lasting with a "wash-out" period of 17 weeks evaluated a group of 23 people over the age of 50, who were subjects with presbyopia and burdened by prolonged work in front of screen monitors. The group of volunteers was recruited from people who perform white-collar jobs on a daily basis. The effects of the test substances contained in the preparation on visual acuity for distance and near, sense of contrast for distance and near, intraocular pressure, and conjunctival lubrication, tested by Schirmer test, LIPCOF index and TBUT test, and visual field test were evaluated. Anthocyanins (including cyanidin 3-O-galactoside, delphinidin 3-O-arabinoside, cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, cyanidin 3-O-arabinoside) and iridoids (including loganin, sweroside, loganic acid) were identified as substances present in the extract obtained by HPLC-MS. The preliminary results showed that the composition of AKB applied orally does not change visual acuity in the first 6 weeks of administration. Only in the next cycle of the study was an improvement in near visual acuity observed in 92.3% of the patients. This may indicate potential to correct near vision in presbyopic patients. On the other hand, an improvement in conjunctival wetting was observed in the Schirmer test at the beginning of week 6 of administration in 80% of patients. This effect was weakened in subsequent weeks of conducting the experiment to 61.5%. The improvement in conjunctival hydration in the Schirmer test shows the potential beneficial effect of the AKB formulation in a group of patients with dry eye syndrome. This is the first study of a preparation based on natural, standardized extracts of chokeberry, honeysuckle berry, and bilberry. Preliminary studies show an improvement in near visual acuity and conjunctival hydration on the Schirmer test, but this needs to be confirmed in further studies.

Effect of Drying Methods on Chemical and Sensory Properties of Cannabis sativa Leaves.

Hemp is used as a source of fiber, oil and bioactive substances including volatile and cannabinoid-containing substances. This paper presents, for the first time, results on the evaluation of drying methods (convective, vacuum-microwave and combined convective pre-drying and vacuum-microwave finishing drying) of hemp leaves on the qualitative and quantitative changes in secondary metabolites, including essential oils, cannabinoids and sterols. A ranking and descriptive test of hemp leaves was also performed. Drying kinetics was presented using three models, including logarithmic, Midilli and modified Page. The SPME-Arrow technique was used to determine 41 volatile compounds, of which caryophyllene, ß-myrcene and α-humulene were dominant in dried and fresh leaves. Regarding the essential oils obtained, 64 were identified, with caryophyllene, humulene epoxide II and limonene being the dominant ones. For preserving the highest amount of oils, the best method was the convective pre-drying followed by vacuum-microwave finishing drying (CD60-VMD) combined method, where the retention of volatile compounds was 36.08%, whereas the CD70 and 240-VMD methods resulted in the highest loss of 83%. The predominant cannabinoids in fresh hemp leaves were CBDA 6.05 and CBD 2.19 mg g-1. Drying caused no change in the cannabinoid profile of the plant material. ß-Sitosterol, campesterol and lupeol were dominant in the phytosterol and triterpene fractions. No changes in either quality or quantity were observed in any of the variants found.

The iridoid loganic acid and anthocyanins from the cornelian cherry (Cornus mas L.) fruit increase the plasma l-arginine/ADMA ratio and decrease levels of ADMA in rabbits fed a high-cholesterol diet.

BACKGROUND: Although fruit and vegetable-rich diets have beneficial effects on cardiovascular diseases, we have little knowledge of the impact of fruits and their constituents, iridoids and anthocyanins, on the l-arginine-ADMA-DDAH pathway. Our previous study demonstrated the modulation of those factors by the oral administration of the cornelian cherry fruit. HYPOTHESIS/PURPOSE: We have assessed the effects of the oral administration of two main constituents isolated from the cornelian cherry fruit, iridoid loganic acid and anthocyanins, on l-arginine, its derivatives (ADMA, SDMA), metabolites (DMA, l-citrulline), and the hepatic DDAH activity and its isoform expression in rabbits fed a high-cholesterol diet. We have also analyzed eNOS expression in the thoracic aorta as well as the redox status in blood. STUDY DESIGN: In the present study, we used an animal model of diet induced atherosclerosis. For 60 days, white New Zealand rabbits were fed a standard diet, a 1% cholesterol enriched diet, or concomitantly with the investigated substances. l-arginine, ADMA, SDMA, DMA, and l-citrulline were assessed using the LC-MS/MS method. DDAH activity and redox parameters were analyzed spectrophotometrically. DDAH1 and DDAH2 isoform expressions were assessed by western blotting, mRNA expression of eNOS was quantified by real-time PCR. RESULTS: We demonstrated that the administration of loganic acid (20 mg/kg b.w.), and to a lesser extent of anthocyanins (10 mg/kg b.w.), caused an increase in the l-arginine level and the l-arginine/ADMA ratio. Also, both substances decreased ADMA, DMA, and l-citrulline, but not SDMA levels. Anthocyanins, but not loganic acid, enhanced the activity of DDAH in the liver. Anthocyanins also significantly enhanced both DDAH1 and DDAH2 expression, while loganic acid to a lesser extent enhanced DDAH1 but not DDAH2 expression. Both loganic acid and anthocyanins pronouncedly increased mRNA expression of eNOS in thoracic aortas. Both loganic acid and anthocyanins reversed the blood glutathione level depleted by dietary cholesterol. Cholesterol feeding decreased the blood GPx level, and the change was not reversed by anthocyanins or loganic acid. We did not observe any significant differences in the blood levels of MDA or SOD among the groups. CONCLUSION: Iridoids and anthocyanins may modulate the l-arginine-ADMA pathway in subjects fed a high-cholesterol diet.

Loganic acid and anthocyanins from cornelian cherry (Cornus mas L.) fruits modulate diet-induced atherosclerosis and redox status in rabbits.

BACKGROUND: Cornelian cherry (Cornus mas L.) is a plant growing in southeast Europe, in the past used in folk medicine. There are many previous publications showing the preventive effects of (poly)phenolic compounds, especially anthocyanins, on cardiovascular diseases, but there is a lack of studies comparing the effects of (poly)phenolics and other constituents of fruits. OBJECTIVES: We have attempted to determine if iridoids and anthocyanins from cornelian cherry fruits may affect the formation of atherosclerotic plaques in the aorta as well as lipid peroxidation and oxidative stress in the livers of cholesterol-fed rabbits. MATERIAL AND METHODS: Fractions of iridoids and anthocyanins were analyzed using the high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) methods. Loganic acid (20 mg/kg b.w.) and a mixture of anthocyanins (10 mg/kg b.w.) were administered orally for 60 days to rabbits fed with 1% cholesterol. Histopathological samples of the aortas and the livers were stained with hematoxylin and eosin. Lipid peroxidation (malondialdehyde - MDA) and redox status (glutathione - GSH, glutathione peroxidase - Gpx and superoxide dismutase - SOD) were analyzed using spectrophotometrical methods. RESULTS: Both loganic acid (an iridoid) and a mixture of anthocyanins diminished the formation of atherosclerotic plaques in the aorta. Both substances also diminished lipid peroxidation, measured as a decrease of MDA, and attenuated oxidative stress, measured as an increase of GSH in the livers depleted by cholesterol feeding. Unexpectedly, cholesterol feeding decreased the Gpx activity in the liver, which was reversed by both investigated substances. CONCLUSIONS: We have shown that both iridoids and anthocyanins help prevent fed-induced atherosclerosis, and the consumption of fruits rich in these substances may elicit beneficial effects on the cardiovascular system.

Comparison of Visual Field Measurement with Heidelberg Edge Perimeter and Humphrey Visual Field Analyzer in Patients with Ocular Hypertension.

BACKGROUND: Glaucoma is a group of eye diseases which result in damage to the optic nerve and vision loss. The most important examination in glaucoma patients is visual field assessment. One of the newer perimeters is Heidelberg Edge Perimeter (HEP). OBJECTIVES: The aim of the study was to compare visual field measurements made with Humphrey II 740 Visual Field (Carl Zeiss Meditec) and Heidelberg Edge Perimeter (HEP) (Heidelberg Engineering). FDF stimulus (flicker defined form) in HEP stimulates magnocellular retinal cells, which are the first to be damaged in the early stage of glaucoma. Even a small loss of magnocellular cells may influence HEP visual field. MATERIAL AND METHODS: The observed group consisted of 45 patients (82 eyes), age 60 ± 9.8 years, glaucoma suspects, not treated pharmacologically or surgically before, with intraocular pressure ≥ 22 mm Hg. Visual field values were measured with two different devices: Humphrey II 740 Visual Field (Carl Zeiss Meditec, Jena, Germany) and Heidelberg Edge Perimeter (Heidelberg Engineering, Heidelberg, Germany). The patients were divided into two groups: Group 1 - tested with SITA Standard program on Humphrey perimeter and ASTA Standard HEP, and Group 2 - tested with SITA Fast program on Humphrey perimeter and ASTA Standard on HEP. RESULTS: Few positive ΔMD results (ΔMD = MD HEP - MD HUM) were obtained in Groups 1 and 2, which means that the deviation value on the HEP perimeter was only slightly higher than the mean deviation value on Humphrey. Therefore, one can conclude that HEP perimeter may detect visual field defects with greater precision. The visual field measurements between ASTA Standard on HEP and SITA Standard on Humphrey as well as ASTA Standard on HEP and SITA Fast on Humphrey are not equal: MD values on HEP perimeter are lower than MD on Humphrey, which can mean that HEP perimeter provides more precise results and shows even early visual field lesions. CONCLUSIONS: HEP perimeter measures visual field defects with greater precision so it should be taken into consideration for earlier glaucoma detection in routine ophthalmological diagnosis.

Iridoid-loganic acid versus anthocyanins from the Cornus mas fruits (cornelian cherry): Common and different effects on diet-induced atherosclerosis, PPARs expression and inflammation.

BACKGROUND AND AIMS: Cardiovascular benefits of fruits are attributed mainly to their (poly)phenolic constituents, especially anthocyanins. The main aim of our study is to compare effects of iridoids and anthocyanins from one fruit on diet-induced atherosclerosis. The cornelian cherry is a native or cultivated plant that grows in many European countries, used in cuisine and folk medicine. In our previous study, we showed its constituents and proved that oral administration of lyophilized fruits to hypercholesterolemic rabbits had preventive effects on atherosclerosis through the activation of PPARα expression. In this study, we have compared the effects of the main constituents of the cornelian cherry:iridoid loganic acid and anthocyanins. METHODS: Our experiment followed the model used in our previous study, in which rabbits were fed 1% cholesterol. RESULTS: We showed that both loganic acid (20 mg/kg b.w.) and a mixture of anthocyanins (10 mg/kg b.w.) administered orally for 60 days had a positive impact on dyslipidemia caused by cholesterol-rich diet, although the effects of anthocyanins were more pronounced. Anthocyanins decreased total and LDL-cholesterol and triglycerides and increased HDL-cholesterol. Loganic acid showed similar effects, but only the triglycerides and HDL-cholesterol changes achieved statistical significance. Anthocyanins, and to a lesser extent loganic acid, significantly decreased intima thickness and intima/media ratio in the thoracic aorta. Both substances decrease ox-LDL in the plasma. Anthocyanins significantly increased expression of PPARγ and α in the liver. Loganic acid also increased their expression, but to a lesser extent. Conversely, loganic acid showed pronounced anti-inflammatory effects, decreasing TNF-α and IL-6 activity. CONCLUSIONS: Our results imply that both substances have a positive effect on factors contributing to the development of diet-induced atherosclerosis. Our results also indicate the potential health benefits of fruits containing anthocyanins and iridoids, and support the idea of creating composed phytopharmaceuticals containing both groups of substances.

Application of Cornelian Cherry Iridoid-Polyphenolic Fraction and Loganic Acid to Reduce Intraocular Pressure.

One of the most common diseases of old age in modern societies is glaucoma. It is strongly connected with increased intraocular pressure (IOP) and could permanently damage vision in the affected eye. As there are only a limited number of chemical compounds that can decrease IOP as well as blood flow in eye vessels, the up-to-date investigation of new molecules is important. The chemical composition of the dried Cornelian cherry (Cornus mas L.) polar, iridoid-polyphenol-rich fraction was investigated. Loganic acid (50%) and pelargonidin-3-galactoside (7%) were found as the main components. Among the other constituents, iridoid compound cornuside and the anthocyans cyanidin 3-O-galactoside, cyanidin 3-O-robinobioside, and pelargonidin 3-O-robinobioside were quantified in the fraction. In an animal model (New Zealand rabbits), the influence of loganic acid and the polyphenolic fraction isolated from Cornelian cherry fruit was investigated. We found a strong IOP-hypotensive effect for a 0.7% solution of loganic acid, which could be compared with the widely ophthalmologically used timolol. About a 25% decrease in IOP was observed within the first 3 hours of use.

Heidelberg Edge Perimeter: The New Method of Perimetry.

Glaucoma is an optic nerve neuropathy associated with progressive visual field loss. One of the most frequent eye diseases these days, it is believed to have affected 60 million people worldwide in 2014. Various visual field examination methods are known, from the confrontational test to kinetic and static perimetry. The latest device to access the visual field is the Heidelberg Edge Perimeter (HEP). It is a flicker perimeter, but, unlike others of its kind, it uses a unique stimulus called FDF (Flicker Defined Form). A 5-grade round stimulus is created by reversing the phase of flickering black and white dots, thereby forming illusory outlines. The test uses randomly flickering points in medium illumination (50 cd/m²). The background remains the same during the whole test. Background luminance is 50 cd/m2, the marker showing time is 400 ms, and the frequency is 15 Hz. Current studies show that HEP can detect early visual field loss which remains invisible during a standard visual field test with standard automated perimetry. HEP might also prove useful in the early detection of other diseases connected with visual field loss, for example in neurology.

The influence of new beta-adrenolytics nebivolol and carvedilol on intraocular pressure and iris blood flow in rabbits.

BACKGROUND: The aim of this study was to assess the influence of propranolol, nebivolol, and carvedilol on intraocular pressure and blood flow in vessels of rabbit's (New Zealand White) eyeball. METHODS: The study was carried out on New Zealand white rabbits. Intraocular pressure was measured with the applanation tonometer Möller-Wedel and Icare; blood flow was measured with Doppler Laser Blood Flow Monitor MBD3. RESULTS: Following a single administration into a conjunctival sac, all drugs decreased intraocular pressure. Iris blood flow was decreased following administration of propranol, but increased by nebivolol and carvedilol. After single and repeated oral administration of nebivolol and carvedilol an IOP decrease was demonstrated, but with no effect of all applied doses on iris or retina/choroid blood flow. CONCLUSION: Studies performed on an animal model indicate that it is possible to reduce the intraocular pressure and increase ocular blood flow in humans, following topical administration of carvedilol and nebivolol. Confirmation of those results in clinical trials may lead to development of a new anti-glaucoma treatment. Further clinical studies of long-term nebivolol and carvedilol are recommended. They are necessary for evaluation of usefulness of those drugs for selected groups of patients, for example those with glaucoma and arterial hypertension.

Heidelberg edge perimeter employment in glaucoma diagnosis--preliminary report.

In recent years, the authors have seen huge progress in the diagnosis of eye diseases. One of the new diagnostic devices is HEP (Heidelberg Edge Perimeter) - for early diagnosis of glaucoma and its progression. It combines visual field test and HRT (Heidelberg Retina Tomograph), which allows authors to obtain the image of the mutual relation between the structure and the function of the sight organ. It could be also used to assess patients with impaired retina, optic nerve and neurological deficits. The SAP function is more suitable for the detection and monitoring of neurological deficits, moderately advanced and advanced glaucoma as well as other diseases associated with extensive or deep visual field deficits, such as ischemic optic neuropathy. FDF stimulus was designed specifically to detect early glaucoma-related changes in the visual field. For about a year, the Ophthalmology Clinic in Wroclaw has owned a new, unique HEP perimeter. The authors present examples of patients diagnosed and treated at the Clinic, with respect to whom the perimeter results obtained using Octopus type perimeter and HEP contour perimeter have been compared. This method has its advantages: it is non-invasive, objective, provides the opportunity to repeat and compare results obtained from subsequent tests. The disadvantages are the difficulty in adapting to a new stimulus, which is not a circular light stimulus, but an outline that is hard to notice for some patients. Although according to the manufacturer the testing time should not exceed 4-5 minutes, it takes 14-15 minutes in many patients. The test is not suitable for patients showing lower manual skills and less attention and those who tire out easily. The HEP perimeter is an innovative method for diagnosing the earliest changes in ganglion cells, that is pre-perimetric glaucoma, or when changes in the visual field are undetectable in a standard test.