Objective:

2

To explore and verify the effect and potential mechanism of

Brucea javanica

Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC).

Methods:

2

The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction

Western blot analysis

and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection

surgical resection with chemotherapy

and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups.

Results:

2

After network pharmacology analysis

4 ingredients

82 active compounds

and 92 related genes in YDZI and SMI were screened out. β-Sitosterol

an active ingredient and intersection compound of YDZI and SMI

upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2

P

<

0.01)

downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1

P

<

0.01) in HMECs under oxaliplatin stimulation

and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients

whereas YDZI and SMI ameliorated this injury (

P

<

0.05 or

P

<

0.01).

Conclusions:

2

YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA

PTGS2

ESR1

and CASP9.