Coptisine Alleviates Pristane-Induced Lupus-Like Disease and Associated Kidney and Cardiovascular Complications in Mice

Abstract

Systemic lupus erythaematosus (SLE) is a chronic multi-system autoimmune disease with a high prevalence of kidney and cardiovascular complications. Considering that Rho-associated coiled-coil-containing protein kinases (ROCKs) play important roles in SLE, inflammation, and cardiovascular disease, we hypothesized that coptisine, which has been found to inhibit ROCKs, may have an effect on SLE. The effect of coptisine was assessed in female BALB/c mice intraperitoneally injected with 0.5 mL of pristane. Serum autoantibodies were tested every month, blood pressure was measured every 2 months, and serum inflammatory markers, spleen pathologic characteristics, renal injury and vascular function were observed at 6 months. The results showed that coptisine decreased the levels of serum autoantibodies and serum inflammatory markers in the SLE mice, improved the pathologic characteristics of the spleen, and simultaneously improved renal injury, decreased inflammatory responses in the kidneys, reduced blood pressure, and improved vascular endothelial function. Western blot assays revealed that inhibiting the activation of the NF-kB and Rho/ ROCK signalling pathways and downstream signalling molecules might be the potential mechanisms of the effects of coptisine. Our findings suggest that therapy with coptisine may be a strategy for preventing SLE and ameliorating associated kidney and cardiovascular complications.

The Material Basis and Mechanism of Xuefu Zhuyu Decoction in Treating Stable Angina Pectoris and Unstable Angina Pectoris

“…The compounds with very good binding capacity are shown in Figure 13 . Among the compounds that bind particularly well to the targets of stable angina, literature mining showed that coptisine (MOL001458) lowered blood pressure and improved endothelial function [ 63 ], while Sigmoidin-B (MOL004935) had an anti-inflammatory activity and antioxidant properties [ 64 ]. Also, Kanzonol B (MOL004815) could regulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglia [ 65 ].…”

Hypertension and endothelial dysfunction in the pristane model of systemic lupus erythematosus

“…In addition, Yan et al demonstrated elevated blood pressure, as measured by tail cuff, in BALB/c mice administered the hydrocarbon oil pristane. The study also showed impaired endothelium‐dependent relaxation in thoracic aorta (Yan et al, 2020). While all of these models have the cardiovascular disease characteristics indicative of SLE, they differ in their various disease manifestations.…”

Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

“…We then showed that ER stress induction by tunicamycin caused endothelial dysfunction and elevated ROS generation, which were reversed by COP. Of note, eNOS activity is reduced by ER-stress-induced apoptosis and inflammation [ 29 ], leading to lowered NO bioavailability and vascular dysfunction [ 30 , 31 , 32 ]. Collectively, our data suggest that COP restores vascular homeostasis in diabetes.…”