Corrective role of endophytic exopolysaccharides from Clerodendrum infortunatum L. on arsenic-induced ovarian steroidogenic dysfunction and associated inflammatory responses.

The present investigation aimed to evaluate the therapeutic potential of exopolysaccharides (EPSs) derived from endophytic fungi against arsenic [As(III)]-mediated metabolic and reproductive ailments. Two endophytic fungi, Diaporthe arengae (CleR1) and Fusarium proliferatum (CleR3), were isolated from Clerodendrum infortunatum (Cle), and used for the extraction of two types of EPSs. GC-MS analysis confirmed the presence of hydroxymethyl furfural (HMF) and α-d-glucopyranose in the EPS1 (CleR1) and EPS2 (CleR3), respectively. FTIR analysis revealed the potential As(III)-chelation properties of both EPSs. EPS1 and EPS2 significantly mitigated As(III)-induced oxidative stress and lipid peroxidation by restoring the activities of antioxidative enzymes. EPSs successfully corrected the gonadotropin imbalance and steroidogenic alterations. The downregulation of proinflammatory (NF-κB and TNF-α) and proapoptotic (BAX) mediators and the upregulation of antiapoptotic (Bcl-2) markers were also detected following the treatment with EPSs. Histomorphological restoration of reproductive and metabolic organs was also observed in both the EPS groups. Moreover, the As(III)-induced increase in the immunoreactivity of the androgen receptor (AR) was successfully reversed by these EPSs. Molecular docking predicted that HMF and α-d-glucopyranose of EPS1 and EPS2 interact with the active site of AR by limiting its activity. Hence, EPS could be effective for developing new therapeutic strategies for managing As(III) toxicity.