A comprehensive study of Tianma Toutong Tablets from the dual dimensions of quality and efficacy using fingerprint techniques and network pharmacology.

BACKGROUND: The quality of traditional Chinese medicine (TCM) is the prerequisite for ensuring its safe and effective clinical application. With the increasing popularity of TCM worldwide, the quality control of TCM products has become increasingly crucial. Tianma toutong tablet (TMTTT) is mainly used for migraine caused by external wind and cold, blood stasis, or deficiency of blood and nourishment. However, the mechanism of action of TMTTT is still unclear, and there has been a lack of in vitro antioxidant activity research and migraine treatment mechanism research. Therefore, it is urgent to establish a set of comprehensive and effective evaluation methods. RESULTS: three fingerprint profiles were established using HPLC, UV, and DSC analysis methods, and established three digital parameters simple complexity index (SX), simple clarity index (SY), simple complexity clarity ratio (Sω), 22 batches of samples were evaluated using a comprehensive linear quantitative fingerprint method (CLQFM). In addition, the antioxidant activity of the samples was determined using the DPPH method, and the relationship between fingerprint peaks in different fingerprints and antioxidant capacity was explored using Pearson correlation coefficients. Finally, network pharmacological research was conducted to investigate the potential targets, compounds, and pathways involved in the treatment of migraines with TMTTT. The results showed that the 22 batches of samples were classified into different quality grades. TMTTT exhibited good antioxidant activity, the fingerprint-efficacy relationship showed that gastrodin, chlorogenic acid, ferulic acid, imperatorin and isoimperatorin had strong antioxidant capacity, providing directions for the identification of active compounds. A total of 36 core targets were identified and screened by network pharmacology, which AKT serine/threonine kinase 1 (AKT1), albumin (ALB), insulin (INS), tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 (IL-6), and compounds such as ß-sitosterol, chrysophanol, vanillin are the key to the treatment of migraine, providing references for subsequent clinical research and new drug development. SIGNIFICANCE: This study examined the consistency of the quality of TMTTT and the mechanism of action in treating migraines from both quality and efficacy perspectives, providing a favorable direction for further research on TMTTT and offering new ideas for the quality control of TCM compound formulations.

Cerebral iron deficiency may induce depression through downregulation of the hippocampal glucocorticoid-glucocorticoid receptor signaling pathway.

BACKGROUND: Iron is a trace essential element to sustain the normal neurological function of human. Many researches had reported the involvement of iron deficiency (ID) in neural development and cognitive functions. However, the role of ID in pathogenesis of depression and its underlying mechanism are still unclear. METHODS: In this study, we first used chronic unpredicted mild stress (CUMS) and iron deprivation mouse models to clarify the pathogenesis role of cerebral ID in depression. Then the role of hippocampal glucocorticoid (GC)-glucocorticoid receptor (GR) pathway in cerebral ID induced depression were elucidated in iron deprivation mice and iron deficiency anemia patients. RESULTS: Our results revealed that both CUMS and iron deprivation could induce cerebral ID in mice, and combination of iron deprivation and CUMS could accelerate the onset and aggravate the symptoms of depression in mice. In hippocampus, ID led to neuronal injury and neurogenesis decrease, which might be related to downregulation of GC-GR signaling pathway caused GR dysfunction, thereby inhibiting the negative feedback regulation function of hippocampus on hypothalamic-pituitary-adrenal (HPA) axis. Moreover, the overactivity of HPA axis in iron deprivation mice and iron deficiency anemia patients also confirmed GR dysfunction. LIMITATIONS: Iron deprivation led to food and water intake decrease of mice, which may affect the behavioral test. In addition, we mainly evaluated the role of hippocampal ID in depression, and the number of iron deficiency anemia patients was limited. CONCLUSIONS: Our results identified that cerebral iron homeostasis was a key factor for maintaining mental stability.

Evaluating the spectrum-effect profiling and pharmacokinetics of Tieshuang Anshen Prescription with better sedative-hypnotic effect based on Fe2+ than Hg2.

Although Zhusha Anshen Pill (ZSASP) is a commonly used traditional prescription for insomnia, the safety of cinnabar in the formula has always been controversial since its initial application in medical fields. Here, we developed a new prescription, Tieshuang Anshen Prescription (TSASP), by improving ZSASP with Fe2+ instead of Hg2+. Besides, TSASP was further optimized by establishing and testing the HPLC fingerprint and its sedative-hypnotic effect of formulas with different compatibility ratios and performing correlation spectrum analysis. The safety of TSASP was also evaluated by HE staining of liver and kidney. In addition, a validated and robust UHPLC-MS/MS method was established to demonstrate the pharmacokinetic characteristics of berberine, palmatine, jatrorrhizine, ligustilide, catalpol, loganin, liquiritin and liquiritigenin after oral administration of TSASP. Our study originally provides a new non-toxic prescription, TSASP, with better sedative-hypnotic effect in comparison with ZSASP, revealing that Fe2+ could replace Hg2+ to eliminate its toxicity and play a sedative role. Meanwhile, we believe that our pharmacokinetics results may contribute valuable reference to both TSASP's specific mechanism of action and its further clinical efficacy and effectiveness research.

Optimization of Culture Condition for Ganoderic Acid Production in Ganoderma lucidum Liquid Static Culture and Design of a Suitable Bioreactor.

Ganoderma lucidum, a famous medicinal mushroom used worldwide, is a rich source of triterpenoids which, together with polysaccharides, are believed to be the main effective constituents of G. lucidum. With the increase of market demand, the wild resource is facing serious limitations, and the quality of cultivated fruiting bodies can be seriously affected by the availability of wood resources and by cultivation management practices. In the present study, we aimed to develop an alternative way to produce useful triterpenoids from G. lucidum. We cultured the strain using a two-stage liquid culture strategy and investigated the effects of nitrogen limitation, carbon supply, static culture volume and air supply in the static culture stage on the accumulation of five triterpenoids (GA-P, GA-Q, GA-T, GA-S, GA-R). Our results showed that, under optimized condition, the total yield of the five triterpenoids reached 963 mg/L (as determined by HPLC). Among the five triterpenoids, GA-T accounted for about 75% of the total yield. Besides, a bioreactor suitable for fungal liquid static culture with a 10 L extensible plastic bag shaped culture unit was designed and in which the maximum total yield of the five GAs reached 856.8 mg/L, and the GAs content reached 5.99%. Our results demonstrate the potential of industrial application of G. lucidum culture for the production of triterpenoids, especially GA-T. Air supply significantly improved the accumulation of triterpenoids, and this will provide important clues to understand why more triterpenoids are produced in the mycelia mat under static liquid culture conditions.