Hydroalcoholic Leaf Extract of Isatis tinctoria L. via Antioxidative and Anti-Inflammatory Effects Reduces Stress-Induced Behavioral and Cellular Disorders in Mice

Abstract

Stress that can occur at different levels of a person’s life can cause and exacerbate various diseases. Oxidative stress and inflammation underlie this process at the cellular level. There is an urgent need to identify new and more effective therapeutic targets for the treatment of stress-induced behavioral disorders and specific drugs that affect these targets. Isatis tinctoria L. is a herbaceous species in the Brassicaceae family. Due to its potential antioxidant, nitric oxide- (NO-) inhibiting, anti-inflammatory, and neuroprotective properties, I. tinctoria could be used to treat depression, anxiety, and stress resistance. Hence, the present study is aimed at delineating whether administration of I. tinctoria leaf extract may improve stress-induced disorders in mice. A set of four behavioral tests was selected that together are suitable for phenotyping acute restraint stress-associated behaviors in mice, namely locomotor activity, social integration, dark/light box, and splash tests. The plasma and brains were collected. A brain-derived neurotrophic factor, tumor necrosis factor-alpha, C-reactive protein, corticosterone, NO, reactive oxygen species levels, superoxide dismutase and catalase activity, and ferric-reducing antioxidant power were measured. In mice stressed by immobilization, decreased locomotor activity, anxiety-like behavior, and contact with other individuals were observed, as well as increased oxidative stress and increased levels of nitric oxide in the brain and plasma C-reactive protein. A single administration of I. tinctoria leaf extract was able to reverse the behavioral response to restraint by a mechanism partially dependent on the modulation of oxidative stress, neuroinflammation, and NO reduction. In conclusion, Isatis tinctoria hydroalcoholic leaf extract can reduce stress-induced behavioral disturbances by regulating neurooxidative, neuronitrosative, and neuroimmune pathways. Therefore, it could be recommended for further research on clinical efficacy in depression and anxiety disorder treatment.

Long-COVID post-viral chronic fatigue and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study

“…In chronic fatigue syndrome, depression and GAD, the neurotoxicity theories conceptualize that the effects of neuro-oxidative stress toxicity (OSTOX) coupled with lowered antioxidant (ANTIOX) defenses cause increased neurotoxicity leading to somatic and affective symptoms [ 30 , 31 ]. This is supported by translational data indicating that blocking nitro-oxidative stress, inflammatory and neurotoxic pathways with selective antioxidative compouds may alleviate depressive-, anxiety-, and chronic fatigue-like behaviors [ 25 , 26 , 30 , 35 – 40 ]. Moreover, in humans, treatment with selected antioxidants improves depression, anxiety and chronic fatigue symptoms [ 41 – 44 ].…”

Multi-omics analysis on the mechanism of the effect of Isatis leaf on the growth performance of fattening sheep

“…The target genes of differential transcripts are mainly enriched in immune regulatory functions, such as defense against viruses and immune responses. ISL has anti-inflammatory and antibacterial functions, and contains various antiviral substances, which can enhance the body's immunity and play an important role in regulating the health of fattening sheep ( 18 , 19 ).…”

“…In addition, ISL is rich in cellulose, which helps gastrointestinal peristalsis, promotes food digestion, increases satiety, and lowers cholesterol, reduces the accumulation of fat in the body. Research has found that the extract of ISL has multiple effects on inhibiting skin fibroblast aging by regulating mTOR-NF-κB-SASP signaling (17), reduces stress-induced behavior and cellular disorders in mice through antioxidant and antiinflammatory effects (18), and the extract also has anti-wrinkle Abbreviations: CON, basal diet; ISL, isatis leaf; DM, dry matter; CP, crude protein; NDF, neutral detergent fiber; ADF, acid detergent fiber; VFA, volatile fatty acid; UPLC-Q-TOF-MS, ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry; ADG, average daily gain; ADFI, average daily feed intake; VIP, variable projection importance; DEG, di erentially expressed gene; GO, Gene ontology; circRNA, circular RNA; lncRNA, long stranded non coding RNA; miRNA, MicroRNA; LPS, lipopolysaccharides. effects (19).…”

“…In addition, ISL is rich in cellulose, which helps gastrointestinal peristalsis, promotes food digestion, increases satiety, and lowers cholesterol, reduces the accumulation of fat in the body. Research has found that the extract of ISL has multiple effects on inhibiting skin fibroblast aging by regulating mTOR-NF-κB-SASP signaling ( 17 ), reduces stress-induced behavior and cellular disorders in mice through antioxidant and anti-inflammatory effects ( 18 ), and the extract also has anti-wrinkle effects ( 19 ). ISL is a common herbaceous plant and Chinese herbal medicine, but there is currently no in-depth study on the growth performance of fattening sheep fed with ISL.…”

In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds

“…Extracts of I. tinctoria have shown strong anti-inflammatory activity [151,152]. Also, the hydroalcoholic leaf extract of I. tinctoria was shown to possess anti-depressive properties and can reduce stressinduced behavioral disorders in mice [153], making qingdainone an interesting candidate ZINC000042890265 (disulfuretin), an aurone derivative, can be found in Cotinus coggygria (known as "smoke tree") [140,141]. Disulfuretin demonstrated strong antioxidative activity in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay with an IC 50 of 9.7 µg/mL [140].…”