Anti-Angiogenic and Vasculoprotective Effect of Punica Granatum Root

AIM AND OBJECTIVE: Angiogenesis is a process of formation of new blood vessels from a pre-existing vasculature. It plays a vital role in embryonic development and numerous pathological conditions including cancer, rheumatoid arthritis, diabetes retinopathy, age related macular degeneration and neurological disorders such as Parkinsonism and Alzheimer‟s disease (Folkman 1990; Folkman 1995). In cancer, the growth and metastasis of tumour are dependent on angiogenesis (Hazel 2003). Cancer cells can generate various pro-angiogenic factors such VEGF, FGF, EGF. These factors promote the migration, proliferation and tube formation of endothelial cells which are essential steps for angiogenesis. The newly formed blood vessels can promote cancer growth by supplying nutrients, oxygen and most importantly facilitate cancer cell metastasis to other localities (Sassa and Hatta 2009; Homayouni 2009). In diabetic patients, hyperglycemia is the triggering factor for tissue alterations such as damage to capillary endothelial cells in the retina and BRB breakdown (Zhang et al. 2014; Brownlee 2005) and one of the key players is vascular endothelial growth factor (VEGF), which promotes angiogenesis, abnormal vascular permeability, and eventually, an inflammatory response. Thus interrupting the process of angiogenesis has become one of the promising approaches in the treatment and prevention of cancer progression and diabetic retinopathy. Drug development from natural products has become a rapidly emerging and highly promising strategy to identify novel anti-angiogenic and anti-tumour agents. Plant derived compounds have played an important role in the development of several clinically useful anticancer agents. Over 62 % of biologically active substances currently used as anticancer agents are derived from natural sources, including plants, marine organism and microorganism. Today over 300 anti-angiogenic molecules targeting different signalling pathways are being tested for their anticancer properties at preclinical and clinical stages (Sassa and Hatta, 2009; Homayouni, 2009). Although the results of clinical trials are encouraging the effects were modest (Lu and Bergers, 2013). Therefore, the search and discovery of novel anti-angiogenic principle that selectively target the angiogenic process could bring hope to millions of sufferers with cancer. Punica granatum belonging to family Punicaceae is more commonly known as pomegranate (Salgado et al. 2006). Punica granatum is a large shrub which grows 12-16 feet, has many spiny branches with lance shaped glossy leaves. The bark of the tree turns gray as the tree ages. The flowers are large, red, white, or variegated having a tubular calyx that eventually becomes the fruit. Pomegranate is considered “A pharmacy unto itself” (Jurenka 2008). Pomegranate has many potential effects including bactericidal, antifungal, antiviral, immune modulation, vermifuge, stimulant, refrigerant, astringent, stomachic, styptic, laxative, diuretic and antihelminthic. It has also been widely used in treatment of cardiovascular diseases, diabetes, diarrhea, dysentery, asthma, bronchitis, cough, bleeding disorders, fever, inflammation, acquired immune deficiency syndrome, dyspepsia, ulcers, bruises, sores, mouth lesions, skin lesions, malaria, prostate cancer, atherosclerosis, hypertension, hyper lipidemia, denture stomatitis, male infertility, vaginitis, erectile dysfunction, Alzheimer's disease, obesity, and neonatal hypoxic-ischemic brain injury (Abdollahzdeh et al 2011; Jurenka 2008; Prakash et al. 2011). Punica granatum Linn roots are found to be rich in ellagitannins, including punicalin and punicalagin, numerous piperidine alkaloids (Tanaka et al. 1986; Neuhofer 1993). They are known for antihelmintic and vermifuge properties (Naqvi et al. 1991) and were found to be effective against melanoma in mice (Suresh et al. 2012). From the literature review, it was noted that fruit extract, peel extract (Dana et al. 2015) and pomegranate juice (Tibullo et al. 2016) possessed ant-angiogenic activity and it was noted that very limited study has been carried out in roots of Punica granatum. Moreover, no scientific report is available regarding antiangiogenic and vasculoprotective potential of Punica granatum roots to the best of my knowledge. Based on this, the present study was planned to evaluate anti-angiogenic and vaculoprotective property of Punica granatum roots in chorioallantoic membrane model. SUMMARY AND CONCLUSION: The effect of punica granatum roots on angiogenesis and vasoprotection was evaluated by chorioallantoic membrance (CAM) model. Powdered Punica granatum roots were extracted with ethanol by hot continuous extraction method. The crude ethanol extract of Punica granatum was subjected to preliminary photochemical examination and quantitative analysis. The free radical scavenging activity of extract was evaluated by DPPH radical scavenging and nitric oxide scavenging activity. It was observed that the extract was rich in alkaloids, flavonoids, tannins, saponins, glycoside and possessed a potent free radical scavenging activity. The extract was screened for angiogenesis modulation in chorioallantoic membranel. In CAM model, a significant decrease in average number of blood vessels was noted in extract treated group compared to vehicle control eggs. The extract was subjected to fractionation using solvents of increasing potency and the fractions were subjected to evaluation of anti-angiogenesis activity in CAM. Among the fractions, the ethyl acetate fraction showed a potent angiogenesis inhibition compared to vehicle control. Based on these results the ethyl acetate fraction was evaluated against glucose induced vascular changed in CAM model. To induce hyperglycemia in developing embryo, a single intravitellus injection of 5 mg glucose/g whole egg was introduced. The treatment groups received ethyl acetate fraction and 5 mg glucose/g whole egg. On day 12 of incubation, the blood glucose levels were measured in blood samples taken from CAM vessels and vascular changes were examined in CAM. Hyperglycaemia with vascular leakage, haemorrhagic spots (microaneurysms), proliferation of new vessels (neovascularization), superficial lesions were spotted in untreated eggs. Ethyl acetate fraction 100 μg showed a significant protection against glucose induced microvascular abnormalities with a significant decrease in blood glucose level and reduced average number of blood vessels. These findings demonstrate the anti-angiogenic and vasculoprotective effect of Punica granatum against hyperglycaemia induced vascular changes in CAM model. In conclusion, root extract of Punica granatum possess a significant angiogenesis inhibition in chorioallantoic membrane assay and vasuloprotective effect in glucose induced vascular change. The possible mechanism of antiangiogenesis and vasoprotective actions are might be due to the presence of active principles that possess a potent antioxidant property of roots, as antioxidants are potent inhibitors of angiogenesis and might be due to the presence of inhibitors that repress the expression of VEGF and VEGF like growth factors thereby inhibiting the formation of new blood vessels and maintaining a vascular stability by inhibiting capillary degeneration and permeability. Thus the isolation of antiangiogenic active principle from Punica granatum roots could bring hope to millions of sufferers with cancer and diabetic retinopathy. Further work is in progress to identify the bioactive compounds and delineate the underlying mechanism of antiangiogenesis and vasoprotection

Study of Serum Magnesium Level in Type 2 Diabetes Mellitus

BACKGROUND : A high prevalence of magnesium deficiency is reported in diabetics. Magnesium depletion has a negative impact on glucose homeostasis and insulin sensitivity in type 2 diabetic patients as well as on the evolution of complications such as retinopathy, nephropathy, neuropathy and arterial atherosclerosis. The aim of this study is to estimate the prevalence of hypomagnesemia in patients with type 2 diabetes mellitus and its correlations with microvascular complications of diabetes like retinopathy, nephropathy, neuropathy. MATERIALS AND METHODS : Patients with type 2 diabetes admitted in Thanjavur Medical College and Hospital over a period of one year between October 2011 to October 2012 formed the study population. The sample size was 100 patients. Serum magnesium concentration was measured by calmagite dye method. RESULTS : The study revealed that prevalence of hypomagnesemia in study subjects was 35%. Sex, age and duration of diabetes were not significant predictors of serum magnesium. Significant association was found between hypomagnesemia and diabetic retinopathy, nephropathy, neuropathy. Significant correlations were not found with co morbidities such as ischemic heart disease and hypertension. Low serum magnesium concentrations are common in type 2 diabetics. Magnesium deficiency is conclusively associated with diabetic retinopathy, nephropathy, neuropathy

A rare cause of dysmenorrhea-accessory cavitated uterine malformation: a case report

Accessory cavitated uterine malformation is a newly recognized mullerian anomaly where the uterine cavity is normal unlike other Mullerian anomalies and hence needs to be described more accurately. These are non-communicating ULMs that occur contiguously along the wall of the uterus. This case report is about a 31 years old female who came with complaints of acute severe dysmenorrhea with a chronic course for the past 2 years and was evaluated for a similar episode in the past where she was diagnosed as fibroid with cystic degeneration and treated with SPRM and OCP which gave no relief from symptoms. With another exacerbation of symptoms two years later, patient was evaluated with an USG suggesting hemorrhagic degeneration in rudimentary horn and gave two differentials- fibroid with cystic degeneration and adenomyoma, wherein the   latter was more likely. As a part of pre-op evaluation, MRI was done. Then came the third differential-ACUM [Accessory cavitated uterine mass]. Patient was counselled about the risk of infertility and uterine rupture in subsequent pregnancy as a post-op complication underwent laparoscopic surgery. Intraoperative and postoperative period was uneventful and HPE of the same confirmed the diagnosis. ACUM is a very treatable cause of severe dysmenorrhea and adequate awareness of this new entity will enable in making the diagnosis early

NIDANA VIVECHANA IN AKAALAJA JARA – REVIEW

Aging is defined as process of growing old, damage to cells, tissues and organs with the passage of time. Ayurveda being ancient system of medicine, clearly described about Jara and defined it as “Vayakrita slathamamsadi avastha” with other Lakshanas like Khalitya, Palitya, Smritinasha, Ksheenabala etc. In the blown up human civilization of present era and in the midst of increased various stress, improper diet, lack of exercise, low quality of food grain etc has adversely affected on the process of aging and may cause signs of premature aging, which is definitely an alarming sign and it may indicate the shorten lifespan. In Ayurveda prevention of disease has given utmost importance. To prevent any of the diseases one must know the causative factors properly, where Nidanaparivarjana is considered as first line of treatment in most of the diseases. “Everyone grows old”, Jara is an inescapable part of life but premature aging is an unnatural, untimely process. Prevention of this Akaalaja jara is possible only by understanding its Nidanas. There are so many internal and external factors which contribute for premature aging and this article is intended to explore those factors like Aharaja, Viharaja, Manasika nidanas to aim for targeted treatment

DEEP LEARNING FEATURE EXTRACTION WITH ENSEMBLE SPECTRAL CLUSTER AND GAUSSIAN MIXTURE FOR MALICIOUS TUMOR DETECTION

Different clustering algorithms produce distinct sub-divisions as they apply disparate partition on the data. Hence, no single clustering algorithm is said to be optimal and therefore resulting in different partitions. To utilize the complementary nature of different partitions, ensemble clustering is used. The work in this paper focuses on producing ensembles through several clustering algorithms that perform feature extraction using deep learning and malicious tumor detection through ensemble cluster. In this study, to improve the performance and reduce the complexity involved in the malicious tumor detection process, Deep Learning Feature Extraction (DLFE) technique is presented. Furthermore, to improve the quality of results obtained, ensemble clusters namely, Normalized Spectral Cluster and Gaussian Mixture technique has been applied to the extracted features. The experimental results of the proposed technique have been evaluated and validated for performance and quality analysis on three datasets based on accuracy, sensitivity, specificity. The experimental results achieved 85.28% accuracy, 70.43% specificity, and 97.19% sensitivity, demonstrating the effectiveness of the proposed technique for identifying normal and abnormal tissues from various test images. The simulation results prove the significance in terms of quality parameters and accuracy in comparison to the state-of-the-art techniques

Antimicrobial and DPPH Free Radical- Scavenging Activities of the Ethanol Extract of Propolis Collected from India

Propolis is a natural product derived from plant resins collected by honey bees. In the present study, ethanolic extract of Propolis (EEP) collected from South India were tested for their antibacterial, antifungal and antioxidative activities. Propolis from Apis mellifera and Trigona sp were collected and compared with the commercial Propolis. EEP from Apis mellifera and commercial Propolis showed higher activity against Staphylococcus aureus and Trigona sp EEP showed higher activity against Candida albicans than commercial. In addition, the total flavanoid and total polyphenol content were analyzed. The chemical compositions of Propolis were identified from Gas Chromatography and Mass Spectrum (GC-MS). The compound 1,4 Di-O-Acetyl-2,3,5-tri-O-Methylribitol (C12H22O7) was found to be first time in the propolis and the rest of the identified compounds were already reported. The results confirms the high DPPH free radical scavenging activity of Indian propolis. Thus Indian propolis, being a rich source of natural antioxidants, may be used in the prevention of various free radicals related diseases

Soil Salinity and Its Management

Soil salinity is a growing threat all over the world due to its toxic effect to reduce soil fertility and water uptake in the crops. An average of 418 million ha soil is saline in nature. Various climatic, geomorphic and rainfall pattern causes which involved in saline soil formation. To reduce the toxic effect proper management of saline soil is required. Irrigation water also a major concern regarding soil salinity management. Saline irrigation water enhances and maintains the severity soil salinity. Crop production aspects root zone salinity provides a strong negative impact on soil fertility. Salinity causes the reduction in nutrient ion, and water uptake has a significant negative effect on crop yields. Soil and water salinity interactions and their influence on crop growth and management of salinity are deliberated in this chapter

Determination of set potential voltages for cucumber mosaic virus detection using screen printed carbon electrode

Cucumber Mosaic Virus (CMV) is a most dangerous pathogen among the cucurbit plant which it striking cucumbers, zucchinis, squashes, watermelons but it also striking to non-cucurbit such as peppers, tobaccos, celeries, beans and tomatoes. Symptoms shown by this virus when they starting to strike are very significant and at the end can kill the hosts they infected. In order to detect these viruses, biosensor such as screen-printed carbon electrode (SPCE) is developed and fixes a set potential voltage is defined using Chronoamperometry (CM) immunosensor technique. For short introduction, CM is a process which is a constant applied potential voltage between the working and reference electrode is maintained in order to create an electrons transfer for the oxidation or reduction species taking place at the surface of working electrode is measured and in this manuscript, complete details about measurement were used to finding the stable set potential voltages will be pointed out

Immunosensor development formatting for tungro disease detection using nano-gold antibody particles application

The plant disease such as Rice tungro disease (RTD) becomes a major problem in rice production and also will effect in the economy loss in the country. Therefore, to tackle this problem at early stages, the immunosensor application is a most reliable sensor nowadays because of advantages towards detecting biological molecule. Thus, in order to deal with immunosensor development, it can be done by undergoing the formation of immunosensor format on screen-printed carbon electrode (SPCE). Results can be elaborated with the potential applications to detect the viruses

Determination of fixed-potential selection using chronoamperometry analysis by screen-printed carbon electrode for rice tungro bacilliform virus (RTBV) detection

This paper describes the analysis for the determination of fixed-potential selection using chronoamperometry technique for the detection of rice tungro bacilliform virus (RTBV). RTBV is one of the viruses that cause Tungro disease in rice plantation where the epidemic has been reported since the mid-1960s. Thus immuno-biosensor developed here can replace traditional and conventional analytical systems. One of the important steps to develop immunosensor is to determine the best potential to use in this system to indicate high percentage of active area in conducting electron and it can be used as the best potential for future immunosensor development