Ellagic Acid Exerts Dual Action to Curb the Pathophysiological Manifestations of Sickle Cell Disease and Attenuate the Hydroxyurea-Induced Myelosuppression in Berkeley Mice.

The use of adjuvant therapy is an attractive approach to manage sickle cell disease (SCD) symptomatically. The present study aimed to investigate the potential of ellagic acid as an adjuvant therapy with hydroxyurea (HU), a key drug for SCD with myelosuppressive toxic effects. A panel of experiments was performed using SCD patient's blood (ex vivo) and transgenic mice model of SCD (in vivo). Ellagic acid exhibited the following beneficial pharmacological actions: (a) potent anti-sickling, polymerization inhibitory, and inherent non-hemolytic activity; (b) pronounced action to abrogate HU-induced neutropenia and to improve key hematological parameters during SCD (RBC, Hb, platelet levels); (c) considerable action to foster vascular tone (L-proline); (d) marked attenuating effect against oxidative stress (nitrotyrosine, hypoxanthine, MDA, GSH); (e) substantial inhibitory role against inflammation (analgesic activity and regulation of hemin, TNF-α, IL-1ß, NF-κB/IκBα); (f) remarkable outcome of declining vaso-occlusive crisis (P-selectin, ERK1/2); (g) notable shielding deed against elevated biochemical marker for organ toxicity (creatinine); (h) noticeably prevented histopathological alterations of the spleen. Additionally, the pharmacokinetic study results of HU in the presence and absence of ellagic acid using a mouse model demonstrate that ellagic acid could be safely co-administered with HU. Overall findings suggest that ellagic acid is a promising candidate for adjuvant therapy in SCD based on its own significant ability against SCD and potentiating capability of HU action via targeting improvement at the various stages of pathophysiological complications during SCD and minimizing HU-induced toxicological manifestations.

Insights into the drug screening approaches in leishmaniasis.

Leishmaniasis, a tropically neglected disease, is responsible for the high mortality and morbidity ratio in poverty-stricken areas. Currently, no vaccine is available for the complete cure of the disease. Current chemotherapeutic regimens face the limitations of drug resistance and toxicity concerns indicating a great need to develop better chemotherapeutic leads that are orally administrable, potent, non-toxic, and cost-effective. The anti-leishmanial drug discovery process accelerated the desire for large-scale drug screening assays and high-throughput screening (HTS) technology to identify new chemo-types that can be used as potential drug molecules to control infection. Using the HTS approach, about one million compounds can be screened daily within the shortest possible time for biological activity using automation tools, miniaturized assay formats, and large-scale data analysis. Classical and modern in vitro screening assays have led to the progression of active compounds further to ex vivo and in vivo studies. In the present review, we emphasized on the HTS approaches employed in the leishmanial drug discovery program. Recent in vitro screening assays are widely explored to discover new chemical scaffolds. Developing appropriate experimental animal models and their related techniques is necessary to understand the pathophysiological processes and disease host responses, paving the way for unraveling novel therapies against leishmaniasis.

Fabrication and characterization of herbal drug enriched Guar galactomannan based nanofibrous mats seeded with GMSC's for wound healing applications.

Electrospun nanofibrous Guar gum/PVA based scaffold matrix incorporated with standardized extracts of four traditional medicinal plants of wound healing repute namely - Acalypha indica (A.i), Aristolochia bracteolata (A.b), Lawsonia inermis (L.i) and Thespesia populnea (T.p) was developed. Combinatorial ratio optimization of the extracts subject to their impact on nanofibre morphology, thermal and swelling stability resulted in a 4:4:1:1 blend of A.i, A.b, T.p and L.i at 20% of the total weight of the polymer mix. Dermal toxicity studies on female wistar rats established the nontoxicity of the generated Scaffold/Dressing. Cutaneous wound healing ability of Mesenchymal Stem Cells (MSC's) is well characterized to amplify their delivery and efficacy at the wound site. Apart from ease of accessibility, increased immune modulation of Gingival MSC's is their clear merit relative to those conventionally sourced from adipose tissues and bone marrow. A population of cells were isolated from discarded sample of human gingiva, following standard procedures and characterized as per minimal criteria as described by International Society for Cellular Therapy's (ISCT). The Cytocompatibility and proliferation of GMSC's were evaluated by MTT and Calcein AM assay demonstrating the viability of the seeded GMSC's up to 6 days. In vivo efficacy of the scaffold with and without GMSC's showed complete restoration of the tissue with minimal scarring. This investigation thus generated an herb drug enriched nanofibrous mat as a dressing and also a skin like scaffold with GMSC's, integrating the biological and technological benefits of herbal medicine and stem cell therapy respectively for skin regenerative applications.