Additionally, berberine synergistically reduces renal fibrosis by suppressing the Notch/Snail pathway (downregulating Jagged1, Notch1, and Snail1) and the RhoA/ROCK pathway (reducing FN accumulation), as well as blocking the SphK1- S1P signaling cascade (decreasing S1P2 receptor expression) (Liu et al., 2012; Yang et al., 2017; Xie et al., 2013; Huang et al., 2012). Here, SPHK1 is linked to renal fibrosis.