Morroniside Inhibits H2O2-Induced Podocyte Apoptosis by Down-Regulating NOX4 Expression Controlled by Autophagy In Vitro

Gao, Xue; Liu, Yi; Wang, Lin; Sai, Na; Liu, Yixiu; Ni, Jian

doi:10.3389/fphar.2020.533809

Cited by 23 publications

(11 citation statements)

References 46 publications

(60 reference statements)

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“…Our experimental results showed that morroniside could activate the autophagic activity of osteoblast precursors, suggesting the promoting effect of morroniside on autophagy during osteoblastogenesis, which is similar to the research results of Gao et al 19 in HO-induced podocytes. However, morroniside can promote both the mTOR activity and autophagy responses of osteoblast precursors.…”

Section: Discussionsupporting

confidence: 91%

Beclin1- and Atg13-dependent autophagy activation and morroniside have synergistic effect on osteoblastogenesis

Zhu

Lin

et al. 2022

Exp Biol Med (Maywood)

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Morroniside is known to improve osteoporosis by promoting osteoblastogenesis. The activation of PI3K/Akt/mTOR signaling is a significant mechanism in morroniside-promoted osteoblastogenesis. It is well known that protective autophagy is an important factor in osteoblastogenesis. However, the activation of mTOR signaling can inhibit autophagy. This study aimed to investigate the relationship between mTOR signaling and autophagy in morroniside-regulated osteoblastogenesis. In this study, we investigated the effect of morroniside on the autophagic activity (LC3 conversion rate, LC3-puncta formation, and autophagosome number) of differentiated osteoblast precursors (MC3T3-E1 cells). Then, we identified the roles of mTOR knockdown in morroniside-regulated alterations of autophagy and osteogenic parameters in MC3T3-E1 cells. Next, mTOR knockdown and overexpression were used to observe the roles of mTOR in morroniside-regulated alterations of autophagic molecules (Atg7, Atg13, and Beclin1). Subsequently, the additional value of the above autophagic molecules on morroniside-regulated osteogenic parameters in MC3T3-E1 cells was analyzed based on lentiviral transduction. Finally, combined with morroniside and TAT-Beclin1, the roles of Beclin1 upregulation in the in vivo effects of morroniside was investigated. Our experimental data showed that morroniside promoted both the mTOR activity and autophagy in MC3T3-E1 cells. Morroniside-upregulated autophagic activity and Atg13 or Beclin1 protein level in MC3T3-E1 cells were enhanced by mTOR knockdown. Furthermore, Morroniside-upregulated Atg13 and Beclin1 expression was reversed by mTOR overexpression. Importantly, autophagy upregulation with overexpression of the autophagic gene, Atg13 or BECN1 (gene form of Beclin1), significantly promoted osteoblastogenesis regulated by morroniside. The promotional effect of morroniside on bone microarchitecture, bone mass, and bone parameters (including trabecular bone area and OCN expression in trabecular bone) in ovariectomized (OVX) mice was enhanced by TAT-Beclin1 administration. In conclusion, the autophagy-enhancing drugs related to Beclin1 or Atg13 may be an effective adjuvant therapy in the treatment of osteoporosis with morroniside.

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Section: Discussionsupporting

confidence: 91%

Beclin1- and Atg13-dependent autophagy activation and morroniside have synergistic effect on osteoblastogenesis

Zhu

Lin

et al. 2022

Exp Biol Med (Maywood)

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“…MR has been documented to possess anti-oxidation, antiinflammation, and anti-apoptosis properties (Gao et al, 2020;Deng et al, 2021;Park et al, 2021). It can exert a neuroprotective role in neurodegenerative diseases by eliminating ROS to enhance the total antioxidant capacity of the rat cortex, thereby preventing nerve cells from H 2 O 2 -induced oxidation injury (Wang et al, 2009;Yao et al, 2009;Zhang et al, 2017c;Li B et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

Zhou

Yao

et al. 2022

Front. Pharmacol.

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Intervertebral disc (IVD) degeneration (IVDD) which is highly prevalent within the elderly population, is a leading cause of chronic low back pain and disability. Nucleus pulposus (NP) cell senescence plays an indispensable role in the pathogenesis of IVDD. Morroniside is a major iridoid glycoside and one of the quality control metrics of Cornus officinalis Siebold & Zucc (CO). An increasing body of evidence suggests that morroniside and CO-containing formulae share many similar biological effects, including anti-inflammatory, anti-oxidative, and anti-apoptotic properties. In a previous study, we reported that Liuwei Dihuang Decoction, a CO-containing formula, is effective for treating IVDD by targeting p53 expression; however, the therapeutic role of morroniside on IVDD remains obscure. In this study, we assessed the pharmacological effects of morroniside on NP cell senescence and IVDD pathogenesis using a lumbar spine instability surgery-induced mouse IVDD model and an in vitro H 2 O 2 -induced NP cell senescence model. Our results demonstrated that morroniside administration could significantly ameliorate mouse IVDD progression, concomitant with substantial improvement in extracellular matrix metabolism and histological grading score. Importantly, in vivo and in vitro experiments revealed that morroniside could significantly reduce the increase in SA-β-gal activities and the expression of p53 and p21, which are the most widely used indicators of senescence. Mechanistically, morroniside suppressed ROS-induced aberrant activation of Hippo signaling by inhibiting Mst1/2 and Lats1/2 phosphorylation and reversing Yap/Taz reduction, whereas blockade of Hippo signaling by Yap/Taz inhibitor-1 or Yap/Taz siRNAs could antagonize the anti-senescence effect of morroniside on H 2 O 2 -induced NP cell senescence model by increasing p53 expression and activity. Moreover, the inhibition of Hippo signaling in the IVD tissues by morroniside was further verified in mouse IVDD model. Taken together, our findings suggest that

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“…are known [16]. Gallic acid is a polyphenol-based compound and is well known for its high antioxidant activity; for loganin and morroniside, studies on the renal protective effect in diabetes are being actively conducted [17][18][19][20][21]. In addition, various effects such as apoptosis and alleviation of inflammation through the NF-κB pathway are known [22,23].…”

Section: Introductionmentioning

confidence: 99%

Corni Fructus Alleviates UUO-Induced Renal Fibrosis via TGF-β/Smad Signaling

Lee

Shin

Roh

2022

BioMed Research International

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Renal fibrosis is a type of chronic kidney disease (CKD) induced by infiltration of inflammatory cells, myofibroblast accumulation, and ECM production in the kidney. From a long time ago, Corni Fructus (CF) is known to supplement the liver and kidney with its tepid properties. In this study, we investigated the renal protective mechanism of CF, which is known to supplement the kidney, in rat model of unilateral ureteral obstruction (UUO). After inducing UUO through surgery, the group was separated ( n = 8 ) and the drug was administered for 2 weeks; normal rats (normal), water-treated UUO rats (control), CF 100 mg/kg-treated UUO rats (CF100), and CF 200 mg/kg-treated UUO rats (CF200). As a result of histopathological examination of kidney tissue with H&E, MT, and PAS staining, it was confirmed that the infiltration of inflammatory cells and the erosion of collagen were relatively decreased in the kidneys treated with CF. Also, CF significantly reduced the levels of MDA and BUN in serum. As a result of confirming the expression of the factors through western blotting, CF treatment significantly reduced the expression of NADPH oxidase and significantly regulated the AMPK/LKB1/NF-κB pathway associated with inflammation. In addition, it downregulated the expression of major fibrotic signaling factors, such as α-SMA, collagen I, MMP-2, and TIMP-1, and significantly regulated the TGF-β1/Smad pathway, which is known as a major regulator of renal fibrosis. Taken together, these findings indicate that CF can alleviate renal fibrosis by regulating the TGF-β1/Smad pathway through inhibition of oxidative stress in UUO.

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Morroniside Inhibits H2O2-Induced Podocyte Apoptosis by Down-Regulating NOX4 Expression Controlled by Autophagy In Vitro

Cited by 23 publications

References 46 publications

Beclin1- and Atg13-dependent autophagy activation and morroniside have synergistic effect on osteoblastogenesis

Beclin1- and Atg13-dependent autophagy activation and morroniside have synergistic effect on osteoblastogenesis

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

Corni Fructus Alleviates UUO-Induced Renal Fibrosis via TGF-β/Smad Signaling

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