Page 129 - 《水产学报》2025年第10期

李森栋，等 水产学报, 2025, 49(10): 109609

[13]
related to the HPA axis, immune regulation, and genoprotective characteristics and so on . Gener-
oxidative stress. Moreover, CRHR1, NR3C2 and ally, these findings of this study provided a compre-
MAPK8 were identified as central nodes in the net- hensive understanding on the molecular mechan-
work. These targets were involved in various stress- isms whereby WS exerts its stress-relieving effects
related pathways, such as inflammatory response in fish. Future studies should focus on verifying
regulation, cortisol receptor signaling, and neuro- these molecular interactions through in vitro and in
protection [57-59] . CRHR1 (Corticotropin-Releasing vivo experiments, as well as assessing the potency
Hormone Receptor 1) as a receptor was involved in of WS in controlling stress-related diseases in fish.

the HPA axis, and played a crucial role in regulat- 3.3 The hepatoprotective effects of WS in dark-
ing cortisol release [60-61] . The interaction between barbel catfish
Withanolides and CRHR1 could modulate cortisol
The liver is an important organ for metabolic
levels, thus may relieve chronic stress in fish in this
and immune functions (Single cell RNA sequen-
study. NR3C2 (Mineralocorticoid Receptor) regu-
cing of human liver reveals distinct intrahepatic
lated the immune response and helped to maintain
macrophage populations). Our study showed that
[58]
fluid balance under stress conditions . Therefore,
hepatocytic vacuolization and lipid accumulation
the interactions of WS compounds with NR3C2 may
were significantly reduced in WS dietary groups.
contribute to immune modulation, mitigating stress
WS dietary increased SOD and catalase activity to
and immunosuppression in fish.
suppress lipid peroxidation, this was consistent with
Notably, in present study, Withanolide A
previous studies in murine models, where ash-
exhibited strong binding affinities to mapk8, a key
wagandha root extract significantly reduced hepatic
regulator of cellular stress responses, and associ-
lipid peroxidation through increasing the activity of
ated with inflammatory pathways and apoptosis.
antioxidant enzymes such as superoxide dismutase
Likewise, after stress stimualtion, mapk8 was signi- [64]
and catalase were increased . The hepatoprotect-
ficantly upregulated (log₂ fold change = 1.78) in the
ive effects of WS are likely due to its bioactive com-
brain tissues of darkbarbel catfish supplemented
pounds, such as Withanolide A and Withanolide D,
with Withanolide A compared with the fish of con-
which could scavenge free radicals and inhibit lipid
trol groups. The increased expression of MAPK8
[65]
peroxidation in liver as reported . Moreover, pro-
could contribute to enhanced neuronal proliferation,
liferating cell nuclear antigen (PCNA) plays a cru-
[62-63]
neuroprotection, and overall resilience . In addi-
cial role in cell proliferation and DNA repair (Pang
tion to these key targets, the network pharmacology
et al., 2024). Immunohistochemical results showed
analysis revealed several downstream signaling
that the expression of PCNA was upregulated in WS
pathways, including the MAPK signaling pathway,
groups, indicating that WS dietary maybe also could
PI3K-Akt signaling pathway, and NF-κB signaling
pathway, these are involved in regulating oxidative promote hepatocyte proliferation in the darkbarbel
stress, inflammation, and immune responses. There- catfish, besides, PCNA was found to maintain gen-
fore, through interacting with these pathways, WS omics integrity via recruiting repair proteins such as
compounds may attenuate the systemic disruptions PARP1, and alleviate cellular stress through effi-
[66]
caused by stress in the liver and brain in fish spe- cient DNA repair mechanisms .
cies. Similarly, WS was previously documented to As a rate-limiting enzyme in protein synthesis,
have the potential as a therapeutic alternative for IARS1 can catalyze the binding of isoleucine to
various disorders because of its activities, such as tRNA with its enzymatic activity directly determin-
immunostimulatory, hepatoprotective, antidepress- ing translation efficiency of mRNAs and cellular
ant, anxiolytic, nootropic, antioxidant, anti-inflam- proliferation capacity. Notably, it was reported that
matory, stress-reducing, anti-tumor, anticonvulsant, IARS1 deficiency could slow down mRNA transla-

中国水产学会主办 sponsored by China Society of Fisheries https://www.china-fishery.cn
19