Abstract
Saikosaponin d (SSd) is one of the main active ingredients in Radix Bupleuri. In our study, network pharmacology databases and metabolomics were used in combination to explore the new targets and reveal the in-depth mechanism of SSd. A total of 35 potential targets were chosen through database searching (HIT and TCMID), literature mining, or chemical similarity predicting (Pubchem). Out of these obtained targets, Neuropilin-1 (NRP-1) was selected for further research based on the degree of molecular docking scores and novelty. Cell viability and wound healing assays demonstrated that SSd combined with NRP-1 knockdown could significantly enhance the damage of HepG2. Metabolomics analysis was then performed to explore the underlying mechanism. The overall difference between groups was quantitatively evaluated by the metabolite deregulation score (MDS). Results showed that NRP-1 knockdown exhibited the lowest MDS, which demonstrated that the metabolic profile experienced the slightest interference. However, SSd alone, or NRP-1 knockdown in combination with SSd, were both significantly influenced. Differential metabolites mainly involved short- or long-chain carnitines and phospholipids. Further metabolic pathway analysis revealed that disturbed lipid transportation and phospholipid metabolism probably contributed to the enhanced anti-hepatoma effect by NRP-1 knockdown in combination with SSd. Taken together, in this study, we provided possible interaction mechanisms between SSd and its predicted target NRP-1.
Highlights
Radix Bupleuri is a common traditional Chinese medicine (TCM), which has been used in China for over 2000 years
Other reported inflammatory and apoptosis-related targets associated with SSd gained satisfactory docking scores, which proved the reliability of targets associated with SSd gained satisfactory docking scores, which proved the reliability of the methods applied
The results showed that NRP-1 knockdown exhibited the lowest metabolite deregulation score (MDS), which demonstrated that the global results showed that NRP-1 knockdown exhibited the lowest MDS, which demonstrated that the metabolic profile would not be severely influenced
Summary
Radix Bupleuri is a common traditional Chinese medicine (TCM), which has been used in China for over 2000 years. Saikosaponin d (SSd), as one of the main active ingredients extracted from. Radix Bupleuri, has been proved to be liver-protective and is used to treat liver fibrogenesis [1], inflammation [2], and viral hepatitis. It was reported that SSd exerted antitumor [3], immunoregulation [4], neuroregulation [5], and anti-allergic activities [6]. On the contrary, studies showed that SSd had toxicity and could induce liver injury [7], hepatocyte or hepatic stellate cells apoptosis [8,9]. The effect of SSd is diverse and the underlying mechanisms remain unclear.
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