Biophysical characterization of the CXC chemokine receptor 2 ligands.

The chemokines of the immune system act as first responders by operating as chemoattractants, directing immune cells to specific locations of inflamed tissues. This promiscuous network is comprised of 50 ligands and 18 receptors where the ligands may interact with the receptors in various oligomeric states i.e., monomers, homodimers, and heterodimers. Chemokine receptors are G-protein coupled receptors (GPCRs) present in the membrane of immune cells. The migration of immune cells occurs in response to a concentration gradient of the ligands. Chemotaxis of neutrophils is directed by CXC-ligand (CXCL) activation of the membrane bound CXC chemokine receptor 2 (CXCR2). CXCR2 plays an important role in human health and is linked to disorders such as autoimmune disorders, inflammation, and cancer. Yet, despite their important role, little is known about the biophysical characteristics controlling ligand:ligand and ligand:receptor interaction essential for biological activity. In this work, we study the homodimers of three of the CXCR2 cognate ligands, CXCL1, CXCL5, and CXCL8. The ligands share high structural integrity but a low sequence identity. We show that the sequence diversity has evolved different binding affinities and stabilities for the CXC-ligands resulting in diverse agonist/antagonist behavior. Furthermore, CXC-ligands fold through a three-state mechanism, populating a folded monomeric state before associating into an active dimer.

Exploring the potentials of Ziziphus mauritiana Lam. seed kernel oil as pharmaceutical oil base: Physicochemical characterization and ketoconazole soap formulation.

Ziziphus mauritiana Lam. (Rhamnaceae) is a large spiny shrub or small tree, native to the Indian subcontinent that can reach a maximum height of 9-15 m. This plant stands as a renowned tropical fruit variety, commonly recognized as the Indian plum, Desert apple, or Indian Jujube. The objective of this study was to examine the standard physicochemical parameters of Z. mauritiana seed kernel oil and to formulate the ketoconazole soap (2 % w/w), using the obtained oil, as a base. The oil was obtained through hexane extraction from the seed kernels. To formulate pharmaceutical ketoconazole soap, Z. mauritiana seed kernel oil was subjected to a basic saponification reaction using potassium hydroxide. All the examined physicochemical parameters, namely acid value (4.71 mg KOH/g), saponification value (229.18 mg KOH/g), peroxide value (4.15 milliequivalents KOH/g), ester value (224.47 mg KOH/g), iodine value (11.19 mg KOH/g), refractive index (1.448), pH (5.93), viscosity (89 cP), and specific gravity (0.912 g/mL) were within the acceptable range for industrial purposes. The examination of quality control parameters, namely drug content (99.49 %), total fatty matter (71.13 %), foam retention time (17.21 min), foam height (18.56 cm), moisture content (9.14 %), and pH (7.16) indicated that the newly formulated ketoconazole soap complied with the acceptable limits. In summary, our research demonstrated the excellent physicochemical stability of Z. mauritiana seed kernel oil and its suitability as a soap base, supporting its promising prospects for cost-effective production of cosmetics, soaps, and shampoos in the pharmaceutical and cosmeceutical industries, reducing reliance on synthetic bases.