Depression is partially caused by inflammation in the central nervous system. Early study demonstrated that musk, glandular secretion from male musk deer, exerted an antidepressant-like effect. The aim of this study was to investigate if muscone, a bioactive ingredient in musk, could ameliorate neuroinflammation and depressive-like behaviors as well as explore the potential action mechanism. Mice were intraperitoneally (i.p.) injected with muscone for 2 weeks prior to administration of lipopolysaccharides (LPS, 1[Formula: see text]mg/kg, i.p.). Pre-treatment with muscone reversed the LPS-induced decrease in body weight within 24[Formula: see text]h and ameliorated depressive-like behaviors shown by sucrose preference, tail suspension test, and forced swimming test. LPS-induced activation of microglial cells and elevation in expression of inflammatory cytokines including IL-1[Formula: see text], RANTES, and MCP-1 in the prefrontal cortex of mice were effectively abrogated by muscone, which significantly down-regulated expression of TLR4, MyD88, Caspase-1, NLRP3, renin, and Ang II. In addition, treatment of BV2 microglia cells with muscone markedly attenuated the LPS-induced rise in protein expression of TLR4, Ang II, and IL-1[Formula: see text]. This study revealed that muscone could ameliorate LPS-induced depressive-like behaviors by repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade.
Depression is partially caused by inflammation in central nervous system. This study investigated the ameliorative effects of phenol glycosides (PG) from Ligustrum lucidum Ait. (Oleaceae) on neuroinflammation and depressive-like behavior in mice hypothalamus as well as the molecular mechanism. Mice were administered with PG extract for 2 weeks prior to treatment with LPS. The mice treated with PG extract showed resistance to LPS-induced reduction in body weight and LPS-induced depressive-like behaviors shown by sucrose preference, tail suspension test, forced swimming test and open field test. LPS-induced activation of microglial cells and elevation in protein expression of inflammatory cytokines including IL-1β, RANTES and MCP-1 in hypothalamus of mice were abrogated by pre-treatment with PG extract. This extract down-regulated expression of TLR4, MyD88, NLRP3, renin and angiotensin II and decreased proportional area of Iba-1 + microglias in hypothalamus. Pretreatment with PG extract inhibited LPS-triggered activation of CaSR/G α11 signaling, stimulated 1-OHase expression in hypothalamus, and enhanced circulating 1,25 (OH) 2 D 3 level. Overall, pre-treatment with PG extract ameliorated LPS-induced depressive-like behaviors by repressing neuroinflammation in mice hypothalamus which was attributed to its suppression on activation of microglia and production of inflammatory cytokines via acting on TLR4 pathway, CaSR and RAS cascade associated with improving vitamin D metabolism. K E Y W O R D S depression, Fructus Ligustri Lucidi, hypothalamus, renin-angiotensin system, vitamin D 1 | INTRODUCTION Depression, one of the most common mental disorders, is considered to be the second leading global cause of years of life lived with disability (Bab & Yirmiya, 2010a), and affects approximately 15-20% of the global population (Zhang & Cheng, 2019). The current prevalence in US is estimated to 10-14 million annually which is more than 5% of the population (Bab & Yirmiya, 2010b). Lifetime and 12-month prevalence of major depressive disorder in China were 6.8 and 3.6%, respectively (Huang, Wang, et al., 2019). Depression has been even implicated as a possible risk factor for other chronic diseases, such as osteopenia characterized by loss of bone minerals (Schweiger et al., 2016). However limited therapeutic options for the treatment of depression are available, creating a great individual and societal burden (Li et al., 2019). Thus, development of novel antidepressant drugs is a pressing task (Zhang & Cheng, 2019).
The molecular pathology involved in the development of depression is complex. Many signaling pathways and transcription factors have been demonstrated to display crucial roles in the process of depression occurrence and development. The multi-components and multi-targets of Traditional Chinese Medicine (TCM) are uniquely advantageous in the prevention and treatment of chronic diseases. This review summarizes the pharmacological regulations of natural products from TCM in the prevention and treatment of depression from the aspects of transcription factors (CREB, NF-κB, Nrf2) and molecular signaling pathways (BDNF-TrkB, MAPK, GSK-3β, TLR-4).
Context Gu-Shu-Kang (GSK) is a clinical traditional Chinese medicine prescription for the treatment of primary osteoporosis. Objective This study investigates the protection of GSK against dexamethasone (Dex)-induced disturbance of musculoskeletal system in male mice and to identify the underlying mechanism. Materials and methods Male C57BL/6 mice in Dex-treated groups were orally administered (i.g.) with vehicle, low dose (0.38 g/kg), middle dose (0.76 g/kg), or high dose (1.52 g/kg) of GSK for 8 weeks. A control group was designed without any treatment. The quadriceps femoris, tibialis anterior and gastrocnemius were harvested. Molecular expression was determined by RT-PCR and immunoblotting. Results Treatment with GSK enhanced weight-loaded swimming time (from 411.7 ± 58.4 s in Dex group to 771.4 ± 87.3 s in GSK-M) and grip strength (from 357.8 ± 23.9 g in Dex group to 880.3 ± 47.6 g in GSK-M). GSK produced a rise in cross-sectional area of myofibers and promoted a switching of glycolytic-to-oxidative myofiber. The administration with GSK affected expression of muscle regulatory factors shown by the down-regulation in MuRF-1 and atrogin-1 and the up-regulation in myogenic differentiation factor (MyoD) and myosin heavy chain (MHC). GSK stimulated tissue IGF-1 signalling pathway (IGF-1R/PI3K/Akt), not only in skeletal muscle but also in bone associated with the amelioration of trabecular bone mineral density and the improvement of osteogenesis. Conclusions These findings revealed the potential mechanisms involved in the beneficial effects of Gu-Shu-Kang on musculoskeletal system in mice with challenging to dexamethasone, and this prescription may have applications in management for muscle atrophy and osteoporosis triggered by glucocorticoid.
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