The Anti-Neuroinflammatory Effect of Fuzi and Ganjiang Extraction on LPS-Induced BV2 Microglia and Its Intervention Function on Depression-Like Behavior of Cancer-Related Fatigue Model Mice

Abstract

The Chinese herb couple Fuzi and Ganjiang (FG) has been a classic combination of traditional Chinese medicine that is commonly used clinically in China for nearly 2000 years. Traditional Chinese medicine suggests that FG can treat various ailments, including heart failure, fatigue, gastrointestinal upset, and depression. Neuroinflammation is one of the main pathogenesis of many neurodegenerative diseases in which microglia cells play a critical role in the occurrence and development of neuroinflammation. FG has been clinically proven to have an efficient therapeutic effect on depression and other neurological disorders, but its mechanism remains unknown. Cancer-related fatigue (CRF) is a serious threat to the quality of life of cancer patients and is characterized by both physical and psychological fatigue. Recent studies have found that neuroinflammation is a key inducement leading to the occurrence and development of CRF. Traditional Chinese medicine theory believes that extreme fatigue and depressive symptoms of CRF are related to Yang deficiency, and the application of Yang tonic drugs such as Fuzi and Ganjiang can relieve CRF symptoms, but the underlying mechanisms remain unknown. In order to define whether FG can inhibit CRF depression-like behavior by suppressing neuroinflammation, we conducted a series of experimental studies in vitro and in vivo. According to the UPLC-Q-TOF/MSE results, we speculated that there were 49 compounds in the FG extraction, among which 30 compounds were derived from Fuzi and 19 compounds were derived from Ganjiang. Our research data showed that FG can effectively reduce the production of pro-inflammatory mediators IL-6, TNF-α, ROS, NO, and PGE2 and suppress the expression of iNOS and COX2, which were related to the inhibition of NF-κB/activation of Nrf2/HO-1 signaling pathways. In addition, our research results revealed that FG can improve the depression-like behavior performance of CRF model mice in the tail suspension test, open field test, elevated plus maze test, and forced swimming test, which were associated with the inhibition of the expression of inflammatory mediators iNOS and COX2 in the prefrontal cortex and hippocampus of CRF model mice. Those research results suggested that FG has a satisfactory effect on depression-like behavior of CRF, which was related to the inhibition of neuroinflammation.

Dual Molecules Targeting 5-HT6 and GABA-A Receptors as a New Approach to Combat Depression Associated with Neuroinflammation

“…The relevance of this approach has been fueled by the fact that inflammatory signaling from microglia might be modulated by GABA-A receptor ligands. , To stimulate an inflammatory response and oxidative stress, the microglia BV-2 cells were subjected to treatment with lipopolysaccharide (LPS) (Figure ). The LPS stimulation assay reflects the clinical settings in which patients exposed to immune activation by bacterial LPS were characterized by depression symptoms . In first-line experiments, we assessed the morphology of microglial cells exposed to LPS and pretreated with selected ligands using fluorescence microscopy.…”

“…The LPS stimulation assay reflects the clinical settings in which patients exposed to immune activation by bacterial LPS were characterized by depression symptoms. 32 In first-line experiments, we assessed the morphology of microglial cells exposed to LPS and pretreated with selected ligands using fluorescence microscopy. Upon stimulation with LPS, we observed that mitochondrial metabolism and respiration in BV-2 cells changed, as there was a clear change in mitochondrial membrane potential (Figure 3B), detected with a fluorescent dye MitoTracker.…”

Kidney tonifying traditional Chinese medicine: Potential implications for the prevention and treatment of osteoporosis

“…Aconiti Lateralis Radix Praeparaia is a Chinese herbal medicine, which possesses the effects of cardiac failure, diarrhea, arthralgia, and edema, but is toxic, and it is frequently combined with Zingiberis Rhizoma to increase efficacy and reduce toxicity ( Peng et al, 2013 ). The Chinese herb pair of Aconiti Lateralis Radix Praeparaia and Zingiberis Rhizoma is a typical TCM combination that is commonly used in the clinic, and it has anti-neuroinflammatory effects and can effectively alleviate tumor-associated fatigue and its depressive symptoms, which is more effective than the two herbal medicines alone ( Yang et al, 2021 ). In addition, the botanical drug combination of Angelica sinensis Radix and Carthami Flos is commonly used to treat blood stasis syndrome ( Yue et al, 2017 ), and the botanical drug couple Salviae miltiorrhizae Radix et Rhizoma and Puerariae Thomsonii Radix is used for the treatment of osteoporosis ( Qin et al, 2020 ), and their effectiveness is superior to that of one natural product alone.…”

Natural product-based bioactive agents in combination attenuate neuroinflammation in a tri-culture model

“…Emerging evidence has shown that some herbal medicines and their bioactive components used in combination can illustrate synergistic and multi-target effects ( Liebner et al, 2018 ; Choi et al, 2011 ; Lin, 2011 ; Calfio et al, 2020 ). Yang et al (2021b) demonstrated that a herbal combination of Aconitum carmichaelii Debx. ( Fuzi ) and Zingiber officinale Rosc.…”