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Item Apoferritin and Dps as drug delivery vehicles: Some selected examples in oncology(Biochimica Et Biophysica Acta (BBA), 2022) Kuruppu, A. I.,; Turyanska, L.; Bradshaw, T. D.; Manickam, S.; Galhena, B. P.; Paranagama, P.; De Silva, R.Background: The ideal nanoparticle should be able to encapsulate either pharmaceutical agents or imaging probes so that it could treat or image clinical tumours by targeting the cancer site efficiently. Further, it would be an added advantage if it demonstrates: small size, built in targeting, biocompatibility and biodegradability. Ferritin, which is an endogenous self-assembling protein, stores iron and plays a role in iron homeostasis. When iron atoms are removed apoferritin (AFt) is formed which consists of a hollow shell where it can be used to load guest molecules. Due to its unique architecture, AFt has been investigated as a versatile carrier for tumour theranostic applications. DNA-binding protein from starved cells (Dps), which also belongs to the ferritin family, is a protein found only in prokaryotes. It is used to store iron and protect chromosomes from oxidative damage; because of its architecture, Dps could also be used as a delivery vehicle. Conclusions: Both these nano particles are promising in the field of oncology, especially due to their stability, solubility and biocompatibility features. Further their exterior surface can be modified for better tumourtargeting ability. More studies, are warranted to determine the immunogenicity, biodistribution, and clearance from the body. General perspective: This review discusses a few selected examples of the remarkable in vitro and in vivo studies that have been carried out in the recent past with the use of AFt and Dps in targeting and delivery of various pharmaceutical agents, natural products and imaging probes in the field of oncology.Item Bioactive Properties and Metabolite Profiles of Endolichenic Fungi in Mangrove Ecosystem of Negombo Lagoon, Sri Lanka(Natural Product Communications, 2022) Weerasinghe, R. H.; Maduranga, K.; Attanayake, R. N.; Shevkar, C.; Kate, A. S.; Weerakoon, G.; Kalia, K.; Paranagama, P.Endolichenic fungi (ELF) serve as a novel source of natural products with distinctive bioactivities. A total of 58 ELF isolated from 29 lichens collected from mangrove and mangrove-associated plants of Negombo lagoon, Sri Lanka were identified using morphological and DNA barcoding techniques. Ethyl acetate extracts of 18 such identified ELF isolates were subjected to in vitro assays to determine antioxidant, anti-inflammatory, tyrosinase inhibitory and antibacterial potency. Liquid chromatography–mass spectrometry (LC–MS) dereplication was conducted on the crude extracts in order to detect the secondary metabolites present. The extracts of Daldinia eschscholtzii and Hypoxylon lividipigmentum had the highest radical scavenging activity with SC50 values 14.27 ±0.24 μg/mL and 18.34±1.37 μg/mL, respectively. D. eschscholtzii also exhibited remarkable anti-inflammatory activity (IC50 7.97 ±0.09 μg/mL). Tyrosinase inhibitory activity was highest in Cytospora xylocarpi (IC50 68.50 ±0.34 μg/mL), while the highest activity against aerobic bacterial species Escherichia coli, Bacillus subtilis, Staphylococcus aureus and the anaerobic bacterial strain Streptococcus mutans was observed in the extracts of Xylaria feegenesis and Curvularia lunata. After a thorough study of the LC–MS profiles, it was found that the chemical profiles of Neofusicoccum occulatum, H. lividipigmentum and Myramaececium rubricosum were previously poorly explored in the literature.Item Cytotoxic Bioxanthracene and Macrocyclic Polyester from Endolichenic Fungus Talaromyces pinophilus: In-Vitro and In-Silico Analysis(Indian J Microbiol, 2022) Shevkar, C.; Armarkar, A.; Weerasinghe, R.; Maduranga, K.; Behera, S.K.; Kalia, Kiran; Paranagama, P.; Kate, A. S.; Pandey, K.Lichens are used in folklore medicines across the globe for wound healing and to treat skin disorders and respiratory diseases. They are an intricate symbiosis between fungi and algae with the domination of fungal counterparts. Recent research studies pointed out that yeast is a third major partner in lichens. Endolichenic fungi (ELF) are also a part of this complex miniature ecosystem. The highly competitive environment of lichens compels ELF to produce toxic metabolites which are comparatively less explored for their chemical diversity and use. Here, we investigated 31 ELF isolated from 32 lichens found on mangrove plants at Puttalam Lagoon of Sri Lanka to find cytotoxic molecules by applying LC-UV-HRMS analysis and in vitro bioassays. The studies resulted in the identification of three potent cytotoxic molecules from endolichenic fungi Talaromyces pinophilus isolated from host lichen Porina tetracerae. The ethyl acetate extract of this fungus showed moderate cytotoxicity against the breast cancer cell line. Chemical characterization of ethyl acetate extract of T. pinophilus produced peniazaphilin B, 152G256a-1, and ES-242-3. The structures of these molecules were confirmed by NMR and MS data. We are reporting ES-242-3 for the first time from the genus Talaromyces and peniazaphilin B and 152G256a-1 from T. pinophilus. The isolated compounds were evaluated for their anticancer potential against breast, oral and cervical cancer cell lines. Compound 152G256a-1 showed potent cytotoxicity against oral cancer (CAL-27 cell line) with an IC50 value of 2.96 ± 0.17 lM while ES-242-3 showed the best activity against breast cancer (MCF-7 cell line) and cervical cancer (HeLa cell line) with IC50 value 14.08 ± 0.2 lM and 4.46 ± 0.05 lM respectively. An insilico analysis was carried out to predict the mechanism of in-vitro activity, drug likeliness, and pharmacokinetic profile of the isolated compounds. The study confirms the potential of ELF T. pinophilus to produce diverse bioactive scaffolds and encourages the researchers to further explore the fungus and its metabolites with newer technologies to produce potent anticancer leads.Item Exploration of Potent Cytotoxic Molecules from Fungi in Recent Past to Discover Plausible Anticancer Scaffolds(Chemistry & Biodiversity, 2022) Shevkar, C.; Pradhan, P.; Armarkar, A.; Pandey, K.; Kalia, K.; Paranagama, P.; Kate, A. S.Fungi are known to produce diverse scaffolds possessing unique biological activities, however, to date, no molecule discovered from a fungal source has reached the market as an anti-cancer drug. Every year number of cytotoxic molecules of fungal origin are getting published and critical analysis of those compounds is necessary to identify the potent ones. A review mentioning the best cytotoxic fungal metabolites and their status in the drug development was published in 2014. In this report, we have included 176 cytotoxic molecules isolated from fungi after 2014 and categorized them according to their potencies such as IC50 values below 1 μM, 1–5 μM, and 5–10 μM. The emphasis was given to those 42 molecules which have shown IC50 less than 1 μM and discussed to a great extent. This review shall provide potent scaffolds of fungal origin which can be given priority in the development as a drug candidate for cancer therapeutics.Item Medicinal plants commonly used against cancer in traditional medicine formulae in Sri Lanka.(Saudi Pharmaceutical Journal, 2019) Kuruppu, A. I.; Paranagama, P.; Goonasekara, C. L.Cancer is a global burden. In low- and middle-income countries around 70% of deaths are due to cancer. For a number of years natural products have been a good source of agents for combatting cancer and plants have played a huge role in anti-cancer product development. For many centuries, indigenous cultures around the world have used traditional herbal medicine to treat a myriad of diseases including cancer. In Sri Lanka, a number of plants have been reported to have anti-cancer properties and some of the commonly used plants are described in this review with an account of their compounds and modes of action. Only a small number of the plants in Sri Lanka have been tested for their bioactivity and more research is required to determine their medicinal activity with the aim of developing novel drugs to fight this disease.Item A secondary metabolite with in vitro radical scavenging activity from endolichenic fungus Daldinia eschscholzii found in lichen, Parmotrema sp. in Sri Lanka(Journal of the National Science Foundation of Sri Lanka, 2020) Manthrirathna, M.; Kandiah, R.; Gunasekera, D.; Samanthi, K.; Welideniya, D.; Maduranga, H.; Paranagama, P.Endolichenic fungi, an unexplored group of microorganisms, are a promising source of bioactive compounds. Secondary metabolites were isolated from the chloroform fraction of crude ethyl acetate extract of endolichenic fungus Daldinia eschscholzii inhabiting the lichen, Parmotrema sp. in Sri Lanka. Two pure compounds, 1 and 2 were isolated and the structures were identified using 1H-, 13C-, 2D- nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) data. Compound 1 did not show any radical scavenging activity in DPPH assay. Compound 2, identified as 8-methoxynaphthalen-1-ol showed strong radical scavenging ability in the DPPH assay with a half maximal inhibitory concentration (IC50) of 10.2 ± 5.8 µg/ mL. The activity of compound 2 was higher than that of the standard, butylated hydroxy toluene (BHT).Item Comparative study on the intervention of ‘Spice’ Mixture (SM) prepared by Natural Food Additives (NFA) alone or intervention of SM with mind calming exercise in the management on female obesity(Indian Journal of Traditional Knowledge, 2020) Manuha, M.I.,; Paranagama, P.; Nageeb, B M.; Iqbal, N.Z.Obesity has become huge health problem in the entire world. In Sri Lanka, the prevalence of obesity is estimated to be 20.3% in men and 36.5% in women in four provinces. Further, the highest prevalence rate in Western Province, especially in Colombo was estimated to be 32.2%, among adults. Obesity is associated with osteoarthritis, obstructive sleep apnea, gall stones, and hiatus hernia. In addition to this obesity is related to numerous other problems, such as menstrual and mental disorders and varicose vein etc. According to the concept of Unani four treatment modalities are there; they are known as Dieto therapy (Ilaj Bil Ghiza), Pharmaco therapy (Ilaj Bil Dawa), Regimental therapy (Ilaj Bit Tadbeer) and Surgery (Ilaj Bil Yad). Biomarkers such as Lipid profile (VLDL, LDL, HDL And Serum triglycerides), Haemoglobin percentage, SGPT and SC (Serum Creatinine) were considered. Blood sample analysis was performed at NATH (National Ayurvedic Teaching Hospital), Borella, National Diabetic Centre, Rajagiriya and Asiri Hospitals Ltd. According to Unani or Greco-Arabic medical concept, improper digestion may play a main role to cause obesity. Improper digestion was corrected by using a ‘spice’ mixture made by Natural Food Additives (NFA), which possesses the actions of carminative, digestive and strengthens the gastro-intestinal tract. The preparation of ‘spice’ mixture included Natural Food Additives (NFA). They are Cumin (Cuminum cyminum), Garlic (Allium sativum), Curry Leaves (Murraya koenigii), Ceylon Cinnamon (Cinnamomum zeylanicum) and Black Pepper (Piper nigram). Studies revealed that waist circumferences (WC) is closely linked to CV disease risk factors. Also, WHO Expert Committee on Obesity in Asian and Pacific populations suggested that revised cutoff points for WC: 90 cm for men and 80 cm for women to identify patients with abdominal obesity. South Asians are more prone to insulin resistance and dyslipidaemic state of abdominal obesity. Study concluded that the intervention of ‘spice’ mixture reduces obesity and the effective mind calm exercises would give more beneficial effect in weight reduction.Item Physicochemical changes of stored cowpea, Vigna unguiculata, treated with selected essential oils to control cowpea bruchid, Callosobruchus maculatus (F.)(Journal of Food, Agriculture & Environment., 2006) Rubasinghege, G.R.S.; Paranagama, P.; Abeywickrama, K.Cowpea (Vigna unguiculata) seeds were treated with essential oils of C. citratus,C. nardus, C. zeylanicum, M. minutum and a standard pesticide (pirimiphos methyl) as fumigant toxicants. At the end of the four month storage period, physical and chemical properties of cowpea from each storage system were analyzed. Variation of physicochemical properties among treated storage systems was insignificant with one exception; 20±5% of moisture was lost in samples treated with essential oils due to absorption of treated oil. Higher protein, fat and dietary fiber contents were reported from essential oil-treated samples compared to those treated with pirimiphos methyl. With lower toxicity to humans and other mammals and less or no significant variation in physicochemical properties, the selected essential oils can be used as fumigant toxicants against Callosobruchus maculatus (F.).Item Phenetic analysis and phytochemical screening of medicinally important Albizia spp. in Sri Lanka(Ceylon Journal of Science (Biological Sciences), 2016) Jayasiri, A.P.A.; Senanayake, S.P.; Paranagama, P.; Amarasinghe, A.P.G.Albizia Durazz. is a genus of 150 species in the tropics and subtropics of the world and belongs to the sub family Mimosaceae in the Family Fabaceae. Of the six species recorded in Sri Lanka, A. lebbeck is used as a shady tree while A. odoratissima is grown mainly for their timber value, However, A. odoratissima and A. lebbeck are found to be used in ayurvedic medicine however, the medicinal properties of these species are not fully understood. A questionnaire survey was carried out using a hundred sample population to identify their medicinal usage. Floral and vegetative characters of the above two Albizia spp. were observed and phenetic relationships were identified. Air dried stem barks of A. odoratissima and A. lebbeck were subjected to sequential solvent extraction using hexane, chloroform, methanol and water, and the crude weight of the yield were obtained. The results revealed that ayurvedic physicians and traditional ayurvedic medical practitioners use A. odoratissima in medicinal preparations whereas the medicinal use of A. lebbeck is not reported. Further, it was revealed that Samanea saman and Adenanthera pavonina are commonly used as substitutes for A. lebbeck. Knowledge of phenetic variation of the two Albizia spp. can be used for accurate identification which prevents adulteration. Highest yield was obtained from the methanolic extracts. These extracts were subjected to preliminary phytochemical screening to assess the occurrence of different phytochemicals. Results have shown the presence of glylcosides, tannins, phenolics, phytosteroids and flavonoids in methanolic extracts A. odoratissima, and A. lebbeck. The present study suggests that further studies should be conducted on the identification of active compounds in these two plant species for their pharmacognostic properties in order to understand their mode of remedial action for ailments.Item Deterrent effects of some Sri Lankan essential oils on oviposition and progeny production of the cowpea bruchid, Callosobruchus maculatus (F.)(Coleoptera; Bruchidae)(2003) Paranagama, P.; Adhikari, C.; Abeywickrama, K.P.; Bandara, P.Essential oils extracted from five plant materials were tested on oviposition and progeny production of F1 adult of cowpea bruchid, Callosobruchus maculatus on cowpea seeds. All oils tested showed a significant inhibition of oviposition and F1 adult emergence compared to the control during no-choice tests. Cymbopogon citratus and C. nardus showed higher effect on oviposition and F1 adult emergence than the essential oils of Alpinia calcarata, Cinnamomum zeylanicum and Murraya koinigii. In the choice test, the percentage ovipositions in all oils treated samples (except 10 mg of M. koinigii) were significantly lower than that of the control and ethanol treated samples. The percentage eggs deposited decreased with increasing doses of the oils ranging from 10 to 160 mg. The percentage of eggs laid was zero in samples treated with 40 mg of C. nardus or A. calcarata, 80 mg of C. citratus and 160 mg of C. zeylanicum. The essential oils of M. koinigii showed the lowest effect on oviposition when compared to other four essential oils.