Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts

Abstract

Background Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT. Methods Rat transplant models were established and divided into SHAM, LT, GAS-L (50 mg/kg GAS), and GAS-H (100 mg/kg GAS) groups. The liver function, inflammatory factors, liver histopathology, survival of rats, number of M2-type macrophages, liver cell apoptosis, and pathway proteins were assayed at 7 days and 14 days after the operations. Results With increasing GAS concentrations, liver function, expression of proinflammatory factors in the liver, and expression of M2-type molecules in macrophages were significantly improved, and the survival time of rats was significantly prolonged (P < 0.05). All rats treated with low or high doses of GAS were judged to have nondeterministic acute rejection. Flow cytometry showed that liver cell apoptosis was decreased significantly in the GAS-L and GAS-H groups after GAS administration compared with apoptosis and differentiation in the LT group (P < 0.05). Expression levels of Caspase-3, Bad, and Bax proteins were decreased, and the expression of the antiapoptotic protein Bcl-2 was increased in the GAS-L and GAS-H groups (P < 0.05). Mechanistically, the ERS-related IRE1α/TRAF2/NF-κB pathway was suppressed by GAS, and GAS acted mainly on intrahepatic macrophages to affect AR and reduce ROS production (P < 0.05). Conclusion GAS ameliorated AR by inhibiting the IRE1α/TRAF2/NF-κB pathway in LT.

Gastrodin provides neuroprotection in models of traumatic brain injury via Nrf2 signaling pathway

“…Oxidative stress causes direct damage to nerve cells through lipid peroxidation and protein oxidation. In addition, it can also mediate mitochondria and other pathways to indirectly induce neuronal apoptosis (Yuan et al, 2019). Interestingly, in this study, gastrodin inhibited TBI-induced neuronal apoptosis in rats.…”

Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex

“…Experimental studies have confirmed acute induction of palmitic acid leads to ER stress and triggers IRE1α to form the IRE1α/TRAF2/IKK complex, which promotes NF-κB activation [ 36 ]. ER stress is also involved in acute rejection of liver transplantation and lung injury via the IRE1α/TRAF2/NF-κB pathway [ 48 , 49 ].…”

Chemistry, Biological Activities, and Pharmacological Properties of Gastrodin: Mechanism Insights

“…[9] In addition to the above findings, gastrodin mitigated cartilage degeneration in rats with osteoarthritis. [84] Yuan et al [10] conducted a study to investigate the impact of gastrodin on acute liver graft rejection in rats. The study indicated that gastrodin diminished the severity of acute liver graft rejection by regulating the IRE1α/TRAF2/NF-kB signaling pathway (Figure 2).…”

“…Gastrodin a phenolic glycoside isolated from Gastrodia elata Blume is considered a traditional Chinese herbal medicine used to manage neurological disorders such as epilepsy, [1,2] dizziness, [3] and stroke. [4] Gastrodin showed antiinflammatory, [5][6][7][8][9][10] antioxidant, [11][12][13][14] anti-cancer, [15][16][17][18][19][20] and neuroprotective properties. [21][22][23][24][25][26][27] In recent years, many studies were conducted on the chemical nature, sources, and characterization of gastrodin, as well as its different biological properties.…”