Structural characterization and protective effect against renal fibrosis of polysaccharide from Ligustrum lucidum Ait.

Tubulointerstitial fibrosis is a chronic and progressive process affecting renal function due to aging (Denic et al., 2016) and/or chronic kidney disease (CKD) (Humphreys, 2018) independent of the underlying etiology (Nastase et al., 2018). A number of recent preclinical advances have clarified the cellular and molecular mechanisms underlying renal fibrosis, such as the signaling of angiotensin II (Ang II), which is the multiple-active peptide in the renin-angiotensin system (RAS). We have ever elucidated that treatment of primary renal tubular cells with Ang II would stimulate the production of profibrogenic factors (Zhang et al., 2010), and that the activity of tissue RAS was induced in the kidney of mice with hyperglycemia-induced nephropathy (Zhang et al., 2008, 2009). Currently there are not yet any targeted therapies that could slow down (Humphreys, 2018) or reverse (Nastase et al., 2018) the development of renal fibrosis.

The significance of natural products as a source of potential drugs has been well recognized (Mahdi et al., 2022; Yousefi et al., 2021). Accumulating evidences have demonstrated the beneficial effects of natural products and functional ingredients on kidney fibrosis (Li et al., 2021, Li et al., 2021; Ren et al., 2016). Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae) which is recorded as a tonic and dietary supplement that possesses the homology of medicine and food (He et al., 2018), has been traditionally used mainly to treat ailments such as menopausal problems, blurred vision, tinnitus, rheumatic pains, palpitations, backache, insomnia as well as to alleviate age-related symptoms (Zhang et al., 2006). It is also a commonly prescribed component in traditional kidney-tonifying herbal formula and even appears as a feed additive in livestock nutrition (Li et al., 2017). As one of the kidney-tonifying herbs and in accordance with the “kidney governing bones” principle of Chinese medicine, emerging pieces of evidence suggested the protective effects of FLL on bone disorders like osteoporosis (Che et al., 2016; Sha et al., 2017). Our study found that treatment of FLL could improve depressive-like behavior by suppressing neuroinflammation via acting on tissue RAS in mice (Feng et al., 2020). Thus, we sought to clarify the effects of FLL on Ang II-induced nephropathy.

The main chemical constituents of FLL include flavonoids, secoiridoids, and triterpenes, which are responsible for the pharmacological activities of FLL (Chen et al., 2013; He et al., 2018). Recently, increasing attention has been paid to polysaccharides as an important source of bioactive natural products. Numerous researches have indicated the bioactivities of natural polysaccharides and promoted the application of polysaccharides in the prevention and treatment of diseases (Yu et al., 2018). One literature has ever reported extraction, isolation, and coagulative activity of polysaccharides from Ligustrum lucidum flowers (Yin et al., 2017). However, whether the natural polysaccharides exist in the fruit of Ligustrum lucidum and whether this component possesses an anti-fibrotic activity remain elusive.

Our purpose in this study was to explore the polysaccharide from FLL, clarify its chemical characteristic, and investigate its anti-fibrotic activity in kidney. A mice model of unilateral ureteral obstruction (UUO) was used to evaluate the nephroprotective effects of FLL polysaccharide since Ang II signaling is one of the most crucial pathological mechanisms for renal fibrosis of UUO mice (Zhang et al., 2010). Additionally, the mouse glomerulus mesangial cells (SV40-MES13) were also applied to investigate the action of FLL polysaccharide on Ang II-evoked fibrosis.

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