BYHWD Alleviates Inflammatory Response by NIK-Mediated Repression of the Noncanonical NF-κB Pathway During ICH Recovery

Abstract

Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that lacks effective treatments. The inflammatory response following ICH is a vital response that affects brain repair and organism recovery. The nuclear factor κB (NF-κB) signaling pathway is considered one of the most important inflammatory response pathways and one of its response pathways, the noncanonical NF-κB signaling pathway, is known to be associated with persistent effect and chronic inflammation. NF-κB–inducing kinase (NIK) via the noncanonical NF-κB signaling plays a key role in controlling inflammation. Here, we investigated potential effects of the traditional Chinese medicine formula Buyang Huanwu Decoction (BYHWD) on inflammatory response in a rat model of ICH recovery by inhibiting the NIK-mediated the noncanonical NF-κB signaling pathway. In the first part, rats were randomly divided into three groups: the sham group, the ICH group, and the BYHWD group. ICH was induced in rats by injecting collagenase (type VII) into the right globus pallidus of rats' brain. For the BYHWD group, rats were administered BYHWD (4.36 g/kg) once a day by intragastric administration until they were sacrificed. Neurological function was evaluated in rats by a modified neurological severity score (mNSS), the corner turn test, and the foot-fault test. The cerebral edema showed the degree of inflammatory response by sacrificed brain water content. Western blot and real-time quantitative reverse transcription PCR tested the activity of inflammatory response and noncanonical NF-κB signaling. In the second part, siRNA treatment and assessment of inflammation level as well as alterations in the noncanonical NF-κB signaling were performed to determine whether the effect of BYHWD on inflammatory response was mediated by suppression of NIK via the noncanonical NF-κB signaling pathway. We show that BYHWD treated rats exhibited: (i) better health conditions and better neural functional recovery; (ii) decreased inflammatory cytokine and the edema; (iii) reduced expression of NIK, a key protein in unregulated the noncanonical NF-κB signaling pathways; (iv) when compared with pretreated rats with NIK targeting (NIK siRNAs), showed the same effect of inhibiting the pathway and decreased inflammatory cytokine. BYHWD can attenuate the inflammatory response during ICH recovery in rats by inhibiting the NIK-mediated noncanonical NF-κB signaling pathway.

Psoralen Promotes Proliferation, Migration, and Invasion of Human Extravillous Trophoblast Derived HTR-8/Svneo Cells in vitro by NF-κB Pathway

“…Since HTR-8/SVneo cells can develop the tube-like formation profile, further studies such as tube formation assay are needed to validate the potential of psoralen for invading trophoblasts to develop vasculogenic mimicry. NF-κB pathway, a well-studied signaling pathway (Xiao et al, 2021), is involved in regulating the invasive function of trophoblast cells (Oh et al, 2020;Wu et al, 2020). For instance, Oh et al (2020) found that autophagy inhibition increased the invasiveness of trophoblastic cell lines by NF-κB activation as evidenced by increased NF-κB activity and p65 expression.…”

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

“…In this study, the modified neurological deficit score (mNSS), corner turning test, and forelimb placement test (FP test) were utilized to assess the short-term neurofunctional behavior of mice (1, 3, 5, and 7 days after ICH) [ 32 , 33 ]. The medium- and long-term neurofunctional behavior of mice was evaluated through the open field test (14 days after ICH) and the Morris water maze test (23–28 days after ICH).…”

The Involvement of Long Non-coding RNA and Messenger RNA Based Molecular Networks and Pathways in the Subacute Phase of Traumatic Brain Injury in Adult Mice

“…The mNSS test was applied to evaluate post-traumatic neurological impairment, as previously described (Xing et al, 2016;Feng et al, 2017;Xiao et al, 2021). The eighteen-point mNSS consists of motor tests (six points), sensory tests (two points), beam balance tests (six points), reflexes absent, and abnormal movements (four points).…”

“…The corner turn test was conducted as previously described (Li et al, 2019(Li et al, , 2020Xiao et al, 2021). Mice would proceed into a corner with an angle of 30 • degrees.…”