Preparation and Characterisation of Liposomes of Bergenia Ciliata Extract and Evaluation of their Hepatoprotective Activity.

Acute liver damage (ALD) can cause biochemical and pathological changes, which can lead to major complications and even death. The goal of the study was to examine the therapeutic efficacy of liposomes of Bergenia ciliata extract against thioacetamide-induced liver damage in rats. Liposomal batches of B. ciliata extract were prepared by altering the kind and amount of phospholipids and characterized through various physiochemical properties such as laser diffraction, TEM, encapsulation efficiency, stability and in-vitro release studies. In-vivo hepatoprotective studies were performed on TAA-induced acute hepatic damage model. Further, in-silico studies of bergenin against the three hepatic damage markers viz. TGF-ß1, TNF-α and interleukin-6 were also performed. Laser diffraction and TEM showed that most stable liposome batch of B. ciliata extract were in the range of 678-1170 nm with encapsulation efficiency of 84.3±3.5. Extract was found to be rapidly dissociated from B. ciliata liposomes in HCl than PBS, according to in-vitro release data. In-vivo data revealed a significant decline in LFT indicators, amelioration of pathological changes and high bergenin bioavailability in the liposomal group. Protective activity of bergenin against ALD targets like TGF-ß1, TNF-α and interleukin-6 was anticipated via molecular docking research. As a result, the current findings of the study indicate that B. ciliata liposomes and bergenin have promising ameliorative potential in the management of ALD.

Olive oil and oleic acid-based self nano-emulsifying formulation of omega-3-fatty acids with improved strength, stability, and therapeutics.

AIM: To develop, characterise, and optimise SNEDDS formulation to enhance organoleptics, bioavailability, physical & oxidative-stability, and extend shelf-life of pure Ω-3-fatty acids oil for use in the food fortification industry as nutraceuticals. METHODS: SNEDDS formulations were prepared using a simple stirring technique and optimised based on in-vitro characterisation. RESULTS: The optimised SNEDDS formulation (F3) had a mean diameter of 52.9 ± 0.4 nm, PDI of 0.229 ± 0.02, zeta potential of -17.3 ± 0.1 mV, cloud temperature of 92 ± 0.2 °C, self-emulsification time of 50 ± 0.2 sec, and stable under accelerated stability conditions. Intestinal permeability study on rat ileum depicted absorption of 88.5 ± 0.2% DHA at 5 h for F3 formulation in comparison to 61.5 ± 0.2% for commercial counterpart. F3 formulation exhibited better therapeutics for melamine-induced cognitive dysfunction. CONCLUSIONS: The developed Ω-3-loaded SNEDDS heralds the future for an efficacious, safer, and higher strength formulation intended as a better substitute for currently available formulations.

Terminal Respiratory Oxidases: A Targetables Vulnerability of Mycobacterial Bioenergetics?

Recently, ATP synthase inhibitor Bedaquiline was approved for the treatment of multi-drug resistant tuberculosis emphasizing the importance of oxidative phosphorylation for the survival of mycobacteria. ATP synthesis is primarily dependent on the generation of proton motive force through the electron transport chain in mycobacteria. The mycobacterial electron transport chain utilizes two terminal oxidases for the reduction of oxygen, namely the bc1-aa3 supercomplex and the cytochrome bd oxidase. The bc1-aa3 supercomplex is an energy-efficient terminal oxidase that pumps out four vectoral protons, besides consuming four scalar protons during the transfer of electrons from menaquinone to molecular oxygen. In the past few years, several inhibitors of bc1-aa3 supercomplex have been developed, out of which, Q203 belonging to the class of imidazopyridine, has moved to clinical trials. Recently, the crystal structure of the mycobacterial cytochrome bc1-aa3 supercomplex was solved, providing details of the route of transfer of electrons from menaquinone to molecular oxygen. Besides providing insights into the molecular functioning, crystal structure is aiding in the targeted drug development. On the other hand, the second respiratory terminal oxidase of the mycobacterial respiratory chain, cytochrome bd oxidase, does not pump out the vectoral protons and is energetically less efficient. However, it can detoxify the reactive oxygen species and facilitate mycobacterial survival during a multitude of stresses. Quinolone derivatives (CK-2-63) and quinone derivative (Aurachin D) inhibit cytochrome bd oxidase. Notably, ablation of both the two terminal oxidases simultaneously through genetic methods or pharmacological inhibition leads to the rapid death of the mycobacterial cells. Thus, terminal oxidases have emerged as important drug targets. In this review, we have described the current understanding of the functioning of these two oxidases, their physiological relevance to mycobacteria, and their inhibitors. Besides these, we also describe the alternative terminal complexes that are used by mycobacteria to maintain energized membrane during hypoxia and anaerobic conditions.