MODULATING THE BIOSYNTHESIS OF A BIOACTIVE STEROIDAL SAPONIN, CHOLESTANOL GLUCOSIDE BY LASIODIPLODIA THEOBROMAE USING ABIOTIC STRESS FACTORS

Objective: The present study investigates the modulation of cholestanol glucoside (CG) biosynthesis by Lasiodiplodia theobromae in response to oxidative, osmotic and heat shock stresses.Methods: The fungal cultures were subjected to oxidative stress by supplementing the culture media with menadione or H2O2 to the desired final concentrations. Osmotic stress was implemented by the addition of the desired concentrations of NaCl or sorbitol. For heat-shock treatments, the fungal cultures were subjected to required temperature variations. Each stress treatment was carried out at different time points so as to include different stages of fungal growth.Results: Oxidative stress enhanced CG yield by the fungus by 1.8-fold (88.3±0.6 mg/l) where as osmotic and heat shock stresses proved to be poor enhancers of CG production.Conclusions: Our findings enable a cost-effective, large scale production of CG by L. theobromae and more over throws light on the possible antioxidant activity of the compound in the organism.Â

Isolation, Purification and Characterization of a Novel Steroidal Saponin Cholestanol Glucoside from Lasiodiplodia theobromae that Induces Apoptosis in A549 Cells

Search for novel anticancer lead molecules continues to be a major focus of cancer research due to the limitations of existing drugs such as lack of tumor selectivity, narrow therapeutic index and multidrug resistance of cancer types. Natural molecules often possess better pharmacokinetic traits compared to synthetic molecules as they continually evolve by natural selection process to interact with biological macromolecules. Microbial metabolites constitute nearly half of the pharmaceuticals in market today. Endophytic fungi, owing to its rich chemical diversity, are viewed as attractive sources of novel bioactive compounds. In the present study, we report the purification and characterization of a novel steroidal saponin, cholestanol glucoside (CG) from Saraca asoca endophytic fungus Lasiodiplodia theobromae. The compound was assessed for its cytotoxic potentialities in six human cancer cell lines, A549, PC3, HepG2, U251, MCF7 and OVCAR3. CG exhibited significant cytotoxicities towards A549, PC3 and HepG2 among which A549 cells were most vulnerable to CG treatment. However, CG treatment exhibited negligible cytotoxicity in non malignant human lung fibroblast cell line (WI-38). Induction of cell death by CG treatment in A549 cells was further investigated. CG induced the generation of reactive oxygen species (ROS) and mitochondrial membrane permeability loss followed by apoptotic cell death. Mitochondrial membrane depolarization and apoptotic cell death in CG treated A549 cells were completely blocked in presence of an antioxidant, N-acetyl cysteine (NAC). Hence it could be concluded that CG initiates apoptosis in cancer cells by augmenting the basal oxidative stress and that the generation of intracellular ROS is crucial for the induction of apoptosis

Phytomedicinal importance of Saraca asoca (Ashoka): an exciting past, an emerging present and a promising future

Since the dawn of civilization, natural resources have remained the mainstay of various remedial approaches of humans vis-a-vis a large number of illnesses. Saraca asoca (Roxb.) de Wilde (Saraca indica L.) belonging to the family Caesalpiniaceae has been regarded as a universal panacea in old Indian Ayurvedic texts and has especially been used to manage gynaecological complications and infections besides treating haemmorhagic dysentery, uterine pain, bacterial infections, skin problems, tumours, worm infestations, cardiac and circulatory problems. Almost all parts of the plant are considered pharmacologically valuable. Extensive folkloric practices and ethnobotanical applications of this plant have even lead to the availability of several commercial S. asoca formulations recommended for different indications though adulteration of these remains a pressing concern. Though a wealth of knowledge on this plant is available in both the classical and modern literature, extensive research on its phytomedicinal worth using state-of-the-art tools and methodologies is lacking. Recent reports on bioprospecting of S. asoca endophytic fungi for industrial bioproducts and useful pharmacologically relevant metabolites provide a silver lining to uncover single molecular bio-effectors from its endophytes. Here, we describe socio-ethnobotanical usage, present the current pharmacological status and discuss potential bottlenecks in harnessing the proclaimed phytomedicinal worth of this prescribed Ayurvedic medicinal plant. Finally, we also look into the possible future of the drug discovery and pharmaceutical R&D efforts directed at exploring its pharma legacy

Variable Effects of Local Management on Coral Defenses Against a Thermally Regulated Bleaching Pathogen

Bleaching and disease are decimating coral reefs especially when warming promotes bleaching pathogens, such as Vibrio coralliilyticus. We demonstrate that sterilized washes from three common corals suppress V. coralliilyticus but that this defense is compromised when assays are run at higher temperatures. For a coral within the ecologically critical genus Acropora, inhibition was 75 to 154% greater among colonies from coral-dominated marine protected areas versus adjacent fished areas that were macroalgae-dominated. Acropora microbiomes were more variable within fished areas, suggesting that reef degradation may also perturb coral microbial communities. Defenses of a robust poritid coral and a weedy pocilloporid coral were not affected by reef degradation, and microbiomes were unaltered for these species. For some ecologically critical, but bleaching-susceptible, corals such as Acropora, local management to improve reef state may bolster coral resistance to global change, such as bacteria-induced coral bleaching during warming events