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Ingelfinger, Rebecca ; Henke, Marina ; Roser, Luise ; Ulshöfer, Thomas ; Calchera, Anjuli ; Singh, Garima ; Parnham, Michael J. ; Geisslinger, Gerd ; Fürst, Robert ; Schmitt, Imke ; Schiffmann, Susanne
Lichen-forming fungi are symbiotic organisms that synthesize unique natural products with potential for new drug leads. Here, we explored the pharmacological activity of six lichen extracts (Evernia prunastri, Pseudevernia furfuracea, Umbilicaria pustulata, Umbilicaria crustulosa, Flavoparmelia caperata, Platismatia glauca) in the context of cancer and inflammation using a comprehensive set of 11 functional and biochemical in vitro screening assays. We assayed intracellular Ca2+ levels and cell migration. For cancer, we measured tumor cell proliferation, cell cycle distribution and apoptosis, as well as the angiogenesis-associated proliferation of endothelial cells (ECs). Targeting inflammation, we assayed leukocyte adhesion onto ECs, EC adhesion molecule expression, as well as nitric oxide production and prostaglandin (PG)E2 synthesis in leukocytes. Remarkably, none of the lichen extracts showed any detrimental influence on the viability of ECs. We showed for the first time that extracts of F. caperata induce Ca2+ signaling. Furthermore, extracts from E. prunastri, P. furfuracea, F. caperata, and P. glauca reduced cell migration. Interestingly, F. caperata extracts strongly decreased tumor cell survival. The proliferation of ECs was significantly reduced by E. prunastri, P. furfuracea, and F. caperata extracts. The extracts did not inhibit the activity of inflammatory processes in ECs. However, the pro-inflammatory activation of leukocytes was inhibited by extracts from E. prunastri, P. furfuracea, F. caperata, and P. glauca. After revealing the potential biological activities of lichen extracts by an array of screening tests, a correlation analysis was performed to evaluate particular roles of abundant lichen secondary metabolites, such as atranorin, physodic acid, and protocetraric acid as well as usnic acid in various combinations. Overall, some of the lichen extracts tested in this study exhibit significant pharmacological activity in the context of inflammation and/or cancer, indicating that the group lichen-forming fungi includes promising members for further testing.
Singh, Garima ; Dal Grande, Francesco ; Divakar, Pradeep K. ; Otte, Jürgen ; Leavitt, Steven D. ; Szczepanska, Katarzyna ; Crespo, Ana ; Rico, Víctor J. ; Aptroot, André ; Cáceres, Marcela Eugenia da Silva ; Lumbsch, Helge Thorsten ; Schmitt, Imke
Species recognition in lichen-forming fungi has been a challenge because of unsettled species concepts, few taxonomically relevant traits, and limitations of traditionally used morphological and chemical characters for identifying closely related species. Here we analyze species diversity in the cosmopolitan genus Protoparmelia s.l. The ~25 described species in this group occur across diverse habitats from the boreal -arctic/alpine to the tropics, but their relationship to each other remains unexplored. In this study, we inferred the phylogeny of 18 species currently assigned to this genus based on 160 specimens and six markers: mtSSU, nuLSU, ITS, RPB1, MCM7, and TSR1. We assessed the circumscription of species-level lineages in Protoparmelia s. str. using two coalescent-based species delimitation methods – BP&P and spedeSTEM. Our results suggest the presence of a tropical and an extra-tropical lineage, and eleven previously unrecognized distinct species-level lineages in Protoparmelia s. str. Several cryptic lineages were discovered as compared to phenotype-based species delimitation. Many of the putative species are supported by geographic evidence.
Vashisht, Rohit ; Mondal, Anupam Kumar ; Jain, Akanksha ; Shah, Anup ; Vishnoi, Priti ; Priyadarshini, Priyanka ; Bhattacharyya, Kausik ; Rohira, Harsha ; Bhat, Ashwini G. ; Passi, Anurag ; Mukherjee, Keya ; Choudhary, Kumari Sonal ; Kumar, Vikas ; Arora, Anshula ; Munusamy, Prabhakaran ; Subramanian, Ahalyaa ; Venkatachalam, Aparna ; S., Gayathri ; Raja, Sweety ; Chitra, Vijaya ; Verma, Kaveri ; Zaheer, Salman ; J., Balaganesh ; Gurusamy, Malarvizhi ; Razeeth, Mohammed ; Raja, Ilamathi ; Thandapani, Madhumohan ; Mevada, Vishal ; Soni, Raviraj ; Rana, Shruti ; Ramanna, Girish Muthagadhalli ; Raghavan, Swetha ; Subramanya, Sunil N. ; Kholia, Trupti ; Patel, Rajesh ; Bhavnani, Varsha ; Chiranjeevi, Lakavath ; Sengupta, Soumi ; Singh, Pankaj Kumar ; Atray, Naresh ; Gandhi, Swati ; Avasthi, Tiruvayipati Suma ; Nisthar, Shefin ; Anurag, Meenakshi ; Sharma, Pratibha ; Hasija, Yasha ; Dash, Debasis ; Sharma, Arun ; Scaria, Vinod ; Thomas, Zakir ; Chandra, Nagasuma ; Brahmachari, Samir K. ; Bhardwaj, Anshu
A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative ‘Connect to Decode’ (C2D) to generate the first and largest manually curated interactome of Mtb termed ‘interactome pathway’ (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.