Total flavonoids of Cynomorium songaricum attenuates cognitive defects in an Aß 1-42 -induced Alzheimer's disease rat model by activating BDNF/TrkB signaling transduction.

Alzheimer's disease (AD) is a degenerative disorder characterized by cognitive dysfunction and BDNF/TrkB is a well-conceived anti-AD signaling. Cynomorium songaricum Rupr. ( C. songaricum ) is a herb with promising neuroprotective effects and the function is majorly attributed to flavonoids. The current study attempted to explore the effects of total flavonoids of C. songaricum (CS) on AD model by focusing on changes in BDNF/TrkB axis. AD model was induced in rats via transcranial injection of Aß 1-42 and AD symptoms treated with CS of three doses. Donepezil was used as the positive control. Changes in rat memory and learning abilities, brain histological, apoptosis, production of neurotransmitters, BDNF/TrkB axis, and apoptosis-related markers were measured. The injection of Aß 1-42 induced cognitive dysfunction in AD rats. The integrity of brain tissue structure was destructed and apoptosis was induced in AD rats, in which was found the increased production of AChE and Aß 1-42 , and decreased production of ChAT, ACH. At the molecular level, the expression of BDNF, TrkB, and Bcl-2 was suppressed, while the expression of Bax, caspase-3, and caspase-9 was induced. After the administration of CS, the memory and learning abilities of rats were improved, the production of neurotransmitter was restored, ordered arrangement of pyramidal cells was retained, and neuron apoptosis was inhibited. The attenuation of Aß 1-42 -indcued impairments was associated with the activation of BDNF/TrkB axis and blockade of apoptosis-related pathways. Collectively, CS can improve learning and memory abilities in Aß 1-42 -induced AD model rats. which may depend on the activation of the hippocampal BDNF/TrkB signaling pathway.

Integrated Metabolites and Transcriptomics at Different Growth Stages Reveal Polysaccharide and Flavonoid Biosynthesis in Cynomorium songaricum.

Cynomorium songaricum is a perennial parasitic herb, and its stem is widely used as a traditional Chinese medicine, which largely relies on bioactive compounds (e.g., polysaccharides, flavonoids, and triterpenes). To date, although the optimum harvest time of stems has been demonstrated at the unearthed stage (namely the early flowering stage, EFS), the accumulation mechanism of polysaccharides and flavonoids during growth stages is still limited. In this study, the physiological characteristics (stem fresh weight, contents of soluble sugar and flavonoids, and antioxidant capacity) at four different growth stages (germination stage (GS), vegetative growth stage (VGS), EFS, and flowering stage (FS)) were determined, transcriptomics were analyzed by illumina sequencing, and expression levels of key genes were validated by qRT-PCR at the GS, VGS, and EFS. The results show that the stem biomass, soluble sugar and total flavonoids contents, and antioxidant capacity peaked at EFS compared with GS, VGS, and FS. A total of 6098 and 13,023 differentially expressed genes (DEGs) were observed at VGS and EFS vs. GS, respectively, with 367 genes co-expressed. Based on their biological functions, 109 genes were directly involved in polysaccharide and flavonoid biosynthesis as well as growth and development. The expression levels of key genes involved in polysaccharides (e.g., GLCs, XTHs and PMEs), flavonoids (e.g., 4CLLs, CYPs and UGTs), growth and development (e.g., AC58, TCPs and AP1), hormones biosynthesis and signaling (e.g., YUC8, AIPT and ACO1), and transcription factors (e.g., MYBs, bHLHs and WRKYs) were in accordance with changes of physiological characteristics. The combinational analysis of metabolites with transcriptomics provides insight into the mechanism of polysaccharide and flavonoid biosynthesis in C. songaricum during growth stages.

Extract of Cynomorium songaricum ameliorates mitochondrial ultrastructure impairments and dysfunction in two different in vitro models of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, but there is still no effective way to stop or slow its progression. Our previous studies demonstrated that extract of Cynomorium songaricum (ECS), a Chinese herbal medicine, had neuroprotective effects in AD models in vivo. However, the pharmacological mechanism of ECS in AD is still unclear. METHODS: To study the mechanisms of action of the effects of ECS on AD, we used Aß25-35- and H2O2-exposed HT22 cells to mimic specific stages of AD in vitro. The mitochondrial membrane potential (MMP), intracellular ATP, intracellular reactive oxygen species (ROS), and expression levels of mitochondrial dynamics-related proteins in each group were examined. Furthermore, we explored the mechanisms by which ECS reduces the phosphorylation of Drp1 at Ser637 and the changes in the concentrations of intracellular calcium ions in the two models after FK506 intervention. RESULTS: The results showed that ECS significantly enhanced the MMP (P < 0.05), increased intracellular ATP levels (P < 0.05) and decreased intracellular ROS levels in the Aß- and H2O2-induced cell models (P < 0.05). Additionally, ECS regulated the expression levels of mitochondrial dynamics-related proteins by reducing the phosphorylation of Drp1 at Ser637 (P < 0.05) and decreasing the expression of Fis1 in the H2O2-induced models (P < 0.05). Further study indicated that ECS reduced the overload of intracellular calcium (P < 0.05). CONCLUSION: Our study results suggest that ECS protects the mitochondrial ultrastructure, ameliorates mitochondrial dysfunction, and maintains mitochondrial dynamics in AD models.

Correlation in Chemical Metabolome and Endophytic Mycobiome in Cynomorium songaricum from Different Desert Locations in China.

Cynomorium songaricum Rupr. is a valuable food and medicinal plant with functions, such as an increase in sexual function, mainly attributed to its complex secondary metabolites. However, the effect of internal microbes on metabolite production in C. songaricum is still largely unclear. In this study, the relationship between endophytes and differential secondary metabolites in C. songaricum from seven major producing regions of China were explored based on established methods of metabolomics and high-throughput sequencing. The results showed that there were 13 different marker metabolites, seven shared fungal OTUs, and numerous unshared OTUs among C. songaricum distributed at different locations in China and identified significant correlations between metabolites and endophytic fungi. Our study revealed that endophytic fungi may be one possible factor that can affect the plant secondary metabolite composition.

Chemical constituents and pharmacologic actions of Cynomorium plants.

The stem of Cynomorium songaricum is a traditional Chinese medicine reputed to have tonic effects. C. coccineum growing in northern Africa and the Mediterranean region is regarded in Arabian medical practice as the "treasure of drugs". The major constituents of Cynomorium plants have been revealed to be phenolic compounds, steroids, triterpenes, etc. Pharmacologic studies showed that the Cynomorium plants had antioxidant, immunity-improving, anti-diabetic, neuroprotective, and other bioactivities. Some chemical constituents in Cynomorium plants are unstable, implying that the chemical components of the herbal medicines produced under different conditions may be variable. This review covers the literature published until December, 2011 and describes the pharmacologic effects and secondary metabolites of Cynomorium species.