Objective. Polyherbal formulations Jathyadi Thailam and Jatyadi Ghritam (JT) are used in Indian traditional medicine for diabetic chronic wounds, fistula, fissure, eczema, and burn management. We aimed to investigate the antibacterial and anti-inflammatory properties of crude hexane and ethanol extracts of JT formulations. Methods. Antibacterial activity of JT extracts was tested to estimate minimum inhibitory concentrations (MICs) against nine reference bacterial strains, including one methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) Pseudomonas aeruginosa, and clinical strains of methicillin-susceptible S.aureus (MSSA), all involved in diabetic foot infection. The anti-inflammatory activity of plant extracts was evaluated in LPS-treated macrophage cells by measuring the mRNA levels and secretion of inflammatory mediators. Results. The antibacterial activity of JT extracts was higher against Gram (+) bacteria, with the MICs varying from 1.95 to 62.5mg/mL. Gram () bacteria were only susceptible to ethanol extracts of JT. Plant extracts were found to be the most active against the reference and clinical strains of MSSA, MRSA, and biofilm-forming S. epidermidis. JT extracts efficiently inhibited in a dose-dependent manner the mRNA expression and protein secretion of proinflammatory cytokines IL-6 and IL-1β, and chemokines MCP-1 and CXCL10 in LPS-challenged macrophages. Conclusion. In the present study, we have shown that extracts of JT formulations possess potent antibacterial and anti-inflammatory properties that could be involved in chronic wound healing activity and has the potential to be used as external add-on therapy in the management of multidrug-resistant bacterial infections at the wound.

Members of the hydroxycarboxylic acid receptor (HCA1-3) family are mainly expressed in adipocytes and immune cells. HCA2 ligand, niacin, has been used for decades as lipid-modifying drug. Recent studies suggest that HCA ligands can be involved in the modulation of inflammatory processes. In this study, we evaluated the effects of HCA1-3 ligands on adipose differentiation and cytokine expression in human adipocytes and macrophages. Simpson-Golabi-Behmel syndrome (SGBS) preadipocytes were induced to differentiate into adipocytes for 8d in the presence or absence of HCA ligands and evaluated for lipid accumulation and adipogenic gene expression. The inhibitory effects of the ligands on the expression and production of cytokines were measured in lipopolysaccharide (LPS)-stimulated adipocytes and THP-1 macrophage cells. Pre-adipocytes treated with HCA ligands showed no changes in the capacity to differentiate into adipocytes and no significant alteration in peroxisome proliferator activated receptor gamma (PPAR gamma) or its target gene expression. HCA2-3 ligands significantly downregulated LPS-induced expression of interleukin (IL)-6 (53-64%), tumor necrosis factor-alpha (TNF-alpha) (55-69%) and IL-8 (51-59%) in adipocytes and macrophages. IL-1 beta inhibition (58-68%) by HCA2-3 ligands was observed only in adipocytes. Furthermore, LPS increased the expression of HCA2-3 in adipocytes and macrophages and this expression was decreased by treatment with their ligands. These results suggest that HCA ligands modulated LPS-mediated pro-inflammatory gene expression in both macrophages and adipocytes without affecting adipogenesis. Therefore, targeting HCA2 and HCA3 would be beneficial in treating inflammation conditions associated with atherosclerosis and obesity.

The paradigm of ligand-receptor interactions postulated as “one compound—one target” has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity. Oxopyranopyrimidine and thioxopyranopyrimidine type compounds have been studied as ligands of the HCA2/GPR109A receptor; nevertheless, they exhibited equal or higher activity towards FFA3/GPR41 and FFA2/GPR43 receptors. S-Alkyl derivatives of pyranopyrimidines that have not yet been studied as ligands of GPCRs were more active towards HCA2/GPR109A and FFA3/GPR41 receptors than towards FFA2/GPR43. Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-α) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. This study revealed groups of compounds possessing multitarget activity towards several receptors. The obtained data could be useful for further development of multitarget ligands.

In the title compound, C₂₅H₂₅NO₅S, which exhibits metabolism-regulating activity, the 1,4-dihydropyridine ring adopts a flattened boat conformation while the cyclohexenone ring is in an envelope conformation. Molecules in the crystal are assembled into C(6) chains along the a-axis direction via N—H...O hydrogen bonds. The thienyl fragment is disordered over two sets of sites in a 0.7220 (19):0.2780 (19) ratio.