RESUMO
Ganoderic acid A (GAA), one of the major triterpenoid components extracted from Ganoderma mushroom has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of GAA on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. The male mice were treated with 25 and 50 mg/mg GAA after stimulated with CCl4. Our results showed that GAA improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. GAA ameliorated CCl4-induced indices of inflammation. GAA suppressed oxidative stress by regulating the glutathione antioxidant system and the thioredoxin antioxidant system. GAA increased the activations of thioredoxin reductase (TrxR), Trx, GSH, SOD, GPx. Furthermore, GAA supplementation inhibited the JAK and STAT3 pathway. GAA inhibited the activations of RhoA, ROCK, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that GAA possesses immune-protective properties through regulating the Trx/TrxR, JAK2/STAT3 and RhoA/ROCK pathways.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Fibrose/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Nefropatias/tratamento farmacológico , Lanosterol/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Fibrose/induzido quimicamente , Fibrose/patologia , Janus Quinase 2/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/patologia , Lanosterol/uso terapêutico , Masculino , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Proteína Smad3/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo , Tiorredoxinas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Quinases Associadas a rho/metabolismoRESUMO
Bixin, an natural carotenoid extracted from the seeds of the Bixa orellana has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of Bixin on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. Our results showed that Bixin improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. Bixin ameliorated CCl4-induced inflammation in kidneys by reducing the levels of TNF-α and IL-1ß. Bixin suppressed oxidative stress by decreasing the MDA level and increasing the activation of SOD, CAT and GPx. Furthermore, Bixin increased the levels of PPAR-γ, NQO1, HO-1 and the nuclear translocation of Nrf2 in the kidneys of mice. Bixin supplementation inhibited the activation of TLR4, MyD88, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that Bixin possesses anti-oxidant, anti-inflammatory and anti-fibrosis properties through regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-ß1/Smad3 pathways.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Carotenoides/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Proteína Smad3/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Tetracloreto de Carbono , Modelos Animais de Doenças , Fibrose , Mediadores da Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos Endogâmicos ICR , Transdução de SinaisRESUMO
Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties. Here, we examined the protective effects of GAS on carbon tetrachloride (CCl4)-induced kidney inflammation and fibrosis in mice, and explored its underlying mechanisms. Our research findings revealed that GAS improved CCl4-induced renal damage in mice. GAS inhibited kidney fibrosis and the deposition of collagen and α-smooth muscle actin (α-SMA). GAS suppressed CCl4-induced inflammation in kidney tissue, as indicated by the decreased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The renoprotective effects of GAS were associated with inhibiting oxidative stress by regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and increasing adenosine 5'-monophosphate activated protein kinase (AMPK) activation. Furthermore, GAS supplementation inactivated the receptor for advanced glycation end products (RAGE) and the high-mobility group box-1 (HMGB1) pathway. GAS inhibited the activation of Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB) and transforming growth factor (TGF)-ß. Collectively, this study clarified that GAS attenuates CCl4-induced kidney inflammation and fibrosis via the AMPK/Nrf2/HMGB1 pathway.