Morroniside Protects Human Granulosa Cells against H2O2-Induced Oxidative Damage by Regulating the Nrf2 and MAPK Signaling Pathways

Abstract

Morroniside is the main ingredient of Cornus officinalis and has a variety of biological activities including antioxidative effects. Ovarian granulosa cells (GCs) are responsible for regulating the development and atresia of follicles, which are susceptible to oxidative stress. In this study, we determined whether morroniside can inhibit the oxidative stress of GCs induced by hydrogen peroxide (H2O2), leading to improved oocyte quality. The oxidative damage and apoptosis of ovarian GCs cultured in vitro were induced by the addition of H2O2. After pretreatment with morroniside, the levels of ROS, MDA, and 8-OHdG in ovarian GCs were significantly decreased. Morroniside significantly upregulated p-Nrf2 and promoted the nuclear translocation of Nrf2, which transcriptionally activated antioxidant SOD and NQO1. In addition, morroniside significantly regulated the levels of apoptosis-related proteins Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 via the p38 and JNK pathways. These results suggest that morroniside can reduce the oxidative damage and apoptosis of ovarian GCs induced by H2O2.

Morroniside Inhibits Inflammatory Bone Loss through the TRAF6-Mediated NF-κB/MAPK Signalling Pathway

“…TRAF6 can activate the NF-κB and MAPK signaling pathways, inhibit the expression of IκBα, and promote the expression of p65 [43]. Research shows that morroniside exerts LPS-induced anti-inflammatory and antioxidant effects by targeting the TLR4/NF-κB and Nrf2/HO-1 signaling pathways in RAW 264.7 macrophages [29] and prevents H2O2 or Aβ1-42-induced apoptosis via attenuating JNK and p38 MAPK phosphorylation [44]. These results indicate that morroniside can play a role in the prevention and treatment of certain diseases through regulating NF-κB/MAPK in cells.…”

Iridoids and active ones in patrinia: A review

“…In addition, 18 other active compounds ( Table 6 ) were obtained from 4 species of Patrinia genus, including Anti-microbial and antiviral (11), Hepatoprotective (4), Enzyme inhibitor (4), Antioxidant (2), Anti-osteoporosis (2), Choleretic (2), Spasmolysis (1), Nephroprotective (1) and Cardioprotective (1), among which, Compounds 51 , 92 and 94 contain multiple activities. The main mechanisms include the regulation of JAK2/STAT3, Nrf2/HO-1, Akt, ERK, NF-κB, JNK signaling pathways [ [11] , [12] , [20] , [26] , [27] , [50] , [51] , [66] , [67] , [68] , [69] , [70] , [71] , [74] , [75] , [76] , [77] , [82] ]. For example, compound 51 activates AKT signal in proximal renal tubular cells [ 31 ] or inhibits JAK2/STAT3 and activates Nrf2/HO-1 signal pathway [ 50 ], it can also reduce the production of tyrosinase, TRP-1 and TRP-2 proteins in melanin cells, while up regulating ERK phosphorylation and down regulating CREB phosphorylation and tyrosinase gene expression [ 51 ].…”

“…Compound 92 reduced the activity of CK-MB, LDH, α -HBDH and AST in AMI rats, and reduced the expression of NF-κB in myocardium [ 67 ]. More, 92 significantly up-regulated p -Nrf2, activated SOD and NQO1, significantly regulated the level of apoptosis related proteins through p38 and JNK pathways, and reduced H 2 O 2 induced oxidative damage and apoptosis of ovarian GCs [ 68 ]. It can also reduce ROS accumulation by regulating Keap1/Nrf2, inhibiting oxidative stress [ 69 ], or activating Nrf2/HO-1 signaling pathway [ 34 ].…”

The effects of natural products and bioactive ingredients of traditional Chinese medicine on apoptosis of ovarian granulosa cells

“…In line with this study, catalpol was found to decrease expression of Bax, caspase‐9, and caspase‐3; reduce ROS generation and malondialdehyde levels; and increase superoxide dismutase activity and glutathione peroxidase expression, which alleviated OS‐induced apoptosis of GCs via activation of the PI3K/AKT/mTOR pathway (Yan et al, 2020). Morroniside was reported to protect against apoptosis of GCs via the PI3K/AKT/mTOR pathway and reduce OS‐induced apoptosis of human GCs via activation of nuclear factor‐like 2 and transportation to the nucleus, followed by upregulation of the antioxidant enzymes superoxide dismutase and quinone reductase 1 (Deng et al, 2021; Ma et al, 2022). Also, the JNK and p38 pathways were involved in the antiapoptosis effects of morroniside (Ma et al, 2022).…”

“…Morroniside was reported to protect against apoptosis of GCs via the PI3K/AKT/mTOR pathway and reduce OS‐induced apoptosis of human GCs via activation of nuclear factor‐like 2 and transportation to the nucleus, followed by upregulation of the antioxidant enzymes superoxide dismutase and quinone reductase 1 (Deng et al, 2021; Ma et al, 2022). Also, the JNK and p38 pathways were involved in the antiapoptosis effects of morroniside (Ma et al, 2022). Astragaloside IV could inhibit apoptosis of GCs and thereby improve female reproductive system damage in diabetic mice (Ren et al, 2021).…”