Nowadays the prevalence of hyperuricemia has significantly increased in which serum uric acid levels are exceeding the normal range. Gout is the predominant clinical implication of the hyperuricemia, but many clinical investigations have confirmed that hyperuricemia is an independent risk factor for cardiovascular disease (CVD), hypertension, diabetes, and many other diseases. The xanthine oxidase (XO) converts hypoxanthine to xanthine and ultimately to uric acid, and the irreversibly accumulated uric acid causes hyperuricemia associated with gout. Hence specific and selective xanthine oxidase inhibitors (XOI) are potentially powerful tools for inactivating target XO in the pathogenic process of hyperuricemia (Gout). The objective of the current study was to overview the various XOI isolated from the microorganisms. Microorganisms have been employed for several decades for the large-scale production of a variety of bio-chemicals ranging from alcohol to antibiotics and as well as enzyme inhibitors. Currently available XOI (allopurinol and febuxostat) for the treatment of gout have been exhibiting serious side effects. Thus, there is a need to search for new molecules to treat hyperuricemia and its associated disorders. At present, microbes have been unexplored in the development of successful products for the management of XO-related diseases. Hence, the present review focused on novel XOI produced from various microbial species such as Actinobacteria, lichens, bacteria, endophytic fungi and mushrooms, which can be expected to play an important role in the ongoing transition from the empirical screening to the real rational drug design.

The present study was designed to investigate the anti-inflammatory potential of Amycolatopsis thermoflava producing 1-O-methyl chrysophanol (OMC), a member of the hydroxyanthraquinone family. The anti-inflammatory potential was evaluated initially through in silico analysis against tumor necrosis factor- α and cyclooxygenase-2. The same activity was further confirmed based on the in vitro protein denaturation method as well as in vivo by a carrageenan-induced paw edema model in rats. The OMC compound was isolated, purified, and characterized from the fermentation broth of Amycoloptosis thermoflava. In vitro data revealed that the OMC possesses significant protein denaturation properties with an IC50 of 63.50±2.19 µg/ml higher than the standard drug, with an IC50 value of 71.42±0.715 µg/ml. The percentage of inhibition in paw swelling was observed to be 40.03±5.5 in OMC-treated group, which is comparable to the standard group (52.8±4.7). The histopathological evaluation and immunohistochemistry revealed the anti-inflammatory potential of OMC.

Hyperuricemia caused by elevated levels of serum uric acid is responsible for implication of gout and other associated disorders that influence the human health. So far, Xanthine oxidase (XO) inhibitors are the choice of first line drugs for the treatment of hyperuricemia. The objective of the present study was to isolate a potent XO inhibitor from the actinobacteria and to evaluate its inhibitory mechanism. Initially, XO was isolated from bovine milk using standard protocol and enzyme kinetics were evaluated. Thereafter, culture filtrates of actinobacteria (Amycolatopsis thermoflavaICTA 103),Streptomyces luteireticuliICTA 16,Streptomyces kurssanoviiICTA165 andAmycolatopsis luridaICTA 194) were screened for XO inhibition usingin vitroqualitative NBT plate assay followed by extraction and purification of potent inhibitor 1-O-methyl chrysophanol (OMC), from the culture filtrate ofAmycolatopsis thermoflavaICTA 103, which belongs to hydroxy anthraquinones (HAQ) family. Further,in silicomolecular model building was performed to study the binding affinity of OMC towards XO followed by quantitativein vitrospectroscopic assays. The molecular building study explored the mechanistic view of binding interaction between inhibitor & enzyme and the results were corroborates with thein vitrokinetic study. Thein vitroresults revealed the significant enzyme inhibition potential of OMC with an IC50andKivalue of 24.8 ± 0.072 µM & 2.218 ± 0.3068 µM respectively. These results are comparable to standard allopurinol, however, more significant than its structural analog, chrysophanol. The kinetic analysis revealed that OMC is a reversible slow binding inhibitor and the Lineweaver - Burkplot analysis showed mixed type inhibition of OMC against XO. These results are in agreement with chrysophanol. Findings of this study proposed a new derivative of HAQ in the pipeline of hyperuricemia therapeutic drug candidates.