Imperatorin inhibits mitogen‐activated protein kinase and nuclear factor kappa‐B signaling pathways and alleviates neuroinflammation in ischemic stroke

Abstract

Aims Microglia‐mediated neuroinflammation plays an important role in the pathological process of ischemic stroke, and the effect of imperatorin on post‐stroke neuroinflammation is not fully understood. Methods Primary microglia were treated with imperatorin for 2 h followed by LPS (100 ng/ml) for 24 h. The expression of inflammatory cytokines was detected by RT‐PCR, ELISA, and Western blot. The activation of MAPK and NF‐κB signaling pathways were analyzed by Western blot. The ischemic insult was determined using a transient middle cerebral artery occlusion (tMCAO) model in C57BL/6J mice. Behavior tests were used to assess the neurological deficits of MCAO mice. TTC staining was applied to measure infract volume. Results Imperatorin suppressed LPS‐induced activation of microglia and pro‐inflammatory cytokines release and attenuated ischemic injury in MCAO mice. The results of transcriptome sequencing and Western blot revealed that downregulation of MAPK and NF‐κB pathways might contribute to the protective effects of imperatorin. Conclusions Imperatorin downregulated MAPK and NF‐κB signaling pathways and exerted anti‐inflammatory effects in ischemic stroke, which indicated that imperatorin might be a potential compound for the treatment of stroke.

Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

“…Imperatorin, known as ammidin, marmelide, and marmelosin, is a naturally occurring active furocoumarin and phytochemical that is mainly found in citrus fruits (such as Citrus grandis and Citrus maxima ) and some species of the genus Angelica that are used as medicine (such as Angelica biserrate , Angelica dahurica , Angelica archangelica , Angelica pubescens and Angelica albicans ). It is known to exert many pharmacological properties, including anti-inflammatory effects on inflammation-associated lung, liver, osteoarthritis, ulcerative colitis, and neuro diseases [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ] as well as anticancer [ 21 , 22 , 23 , 24 ] and antiviral activities [ 25 , 26 , 27 ]. A recent study has shown that imperatorin IMP can ameliorate PS-induced learning and memory deficits through the BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathways and the hypothalamic–pituitary–adrenal axis [ 28 ].…”

Imperatorin inhibits oxidative stress injury and neuroinflammation via the PI3K/AKT signaling pathway in the MPTP-induced Parkinson’s disease mouse

“…As reported, this compound can exert protective functions though its anti-inflammatory and antioxidant actions. For example, imperatorin inhibits the IL-1β-induced iNOS expression in human osteoarthritis chondrocytes [22], suppresses the neuroinflammation in ischemic stroke [23] and reduces the inflammatory response of atherosclerosis in vivo [24]. In the current study, we found that MPTP injection led to significant increases in Iba-1, iNOS, COX-2, TNF-α, IL-1β, IL-6 and MDA levels and decreases in SOD and GSH levels, whereas imperatorin treatment reversed these changes, indicating that imperatorin inhibited the MPTP-induced neuroinflammation and oxidative stress in mice.…”

Imperatorin-Loaded RH60/mPEG–PLLA Micelles for Reversing Tamoxifen Resistance in Breast Cancer

“…Recent pharmacological studies have shown that IMP exhibits a range of physiological activities, including anti-inflammatory, 5 antibacterial, 6 antioxidant, 7 analgesic, 8 cardiovascular protection, 9 antiviral, 10 anticancer, 11 and hepatoprotective effects. 12 Recent studies have shown that IMP possesses the ability to reverse the drug resistance of tumor cells to chemotherapy drugs.…”

“…Among these constituents, imperatorin (IMP), classified as a 6,7-furan coumarin compound, serves as the principal pharmacologically active component of A. dahurica. Recent pharmacological studies have shown that IMP exhibits a range of physiological activities, including anti-inflammatory, antibacterial, antioxidant, analgesic, cardiovascular protection, antiviral, anticancer, and hepatoprotective effects . Recent studies have shown that IMP possesses the ability to reverse the drug resistance of tumor cells to chemotherapy drugs .…”