Tongqiao Huoxue Decoction ameliorates traumatic brain injury-induced gastrointestinal dysfunction by regulating CD36/15-LO/NR4A1 signaling, which fails when CD36 and CX3CR1 are deficient.

AIMS: Gastrointestinal (GI) dysfunction, as a common peripheral-organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti-inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI-induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI-induced GI dysfunction and the underlying mechanism thereof. METHODS: We assessed the protective effects and possible mechanism of TQHXD in treating TBI-induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM). RESULTS: TQHXD administration ameliorated TBI-induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T-regulatory cell (Treg)/T helper 1 cell (Th1 ), as well as Th17 /Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15-lipoxygenase (15-LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD-treated mice. However, insufficiency of both CD36 and (C-X3-C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD. CONCLUSION: TQHXD exerted therapeutic effects on TBI-induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15-LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI-induced GI dysfunction.

[Determination of complexation ability of rhubarb with copper ions by ultra-high performance liquid chromatography].

Gandou decoction (GDD) is a traditional Chinese medicine prescription that has been widely used to treat copper metabolism disorders in China with remarkable clinical effect and lower toxicity. However, evaluation of the complexation ability of copper ions is challenging, which hinders screening and discovery of coordinate active ingredients in GDD. An analytical method is needed to determinate the complexation ability of chemical constituents with copper ions. In this study, a rapid and accurate method based on ultra-high performance liquid chromatography (UHPLC) was developed to determine the complexing ability of rhubarb with copper ions. First, the optimal coordination reaction conditions between active ingredients of rhubarb and copper ions were determined. The samples were separated using an Agilent Eclipse Plus C18 column (50 mm×2.1 mm, 1.8 µm) with 5 µL injection volumes. The mobile phase was gradient eluted with methanol and water containing 0.1% (v/v) phosphoric acid at a flow rate of 0.3 mL/min. The detection wavelength was 254 nm and the column temperature was 30 ℃. Under the optimized chromatographic conditions, the rhubarb constituents were effectively separated. Next, peak areas of rhubarb were calculated before and after the coordination reaction between copper ions. The complexing ability of active ingredients in rhubarb with copper ions was evaluated by calculating the rate of changes of their chromatographic peak areas. Finally, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to identify the coordination active ingredients in rhubarb extract. Focusing on the coordination reaction conditions between active ingredients of rhubarb and copper ions revealed that the active ingredients of rhubarb and copper ions reached equilibrium by coordination reaction at pH 9 for 12 h. Methodological evaluation revealed the good stability and repeatability of the method. Under these conditions, 20 major components of rhubarb were identified by UPLC-Q-TOF-MS. According to the coordination rate of each component and copper ions, eight components with strong coordination were screened out (gallic acid 3-O-ß-D-(6'-O-galloyl)-glucopyranoside, aloe emodin-8-O-ß-D-glucoside, sennoside B, l-O-galloyl-2-O-cinnamoyl-glucoside, chysophanol-8-O-ß-D-(6″-O-acetyl)-glucoside, aloe-emodin, rhein and emodin). The respective complexation rates of the components were 62.50%, 29.94%, 70.58%, 32.77%, 34.61%, 26.07%, 28.73% and 31.78%. Compared with other reported methods, the presently developed method can be used to screen the active ingredients of traditional Chinese medicines that have complexing ability with copper ions, especially in complex mixture systems. This study describes an effective detection technology for evaluating and screening the complexing ability of other traditional Chinese medicines with metal ions.

Therapy of traumatic brain injury by modern agents and traditional Chinese medicine.

Traumatic brain injury (TBI) is the leading cause of disability and death, and the social burden of mortality and morbidity caused by TBI is significant. Under the influence of comprehensive factors, such as social environment, lifestyle, and employment type, the incidence of TBI continues to increase annually. Current pharmacotherapy of TBI mainly focuses on symptomatic supportive treatment, aiming to reduce intracranial pressure, ease pain, alleviate irritability, and fight infection. In this study, we summarized numerous studies covering the use of neuroprotective agents in different animal models and clinical trials after TBI. However, we found that no drug has been approved as specifically effective for the treatment of TBI. Effective therapeutic strategies for TBI remain an urgent need, and attention is turning toward traditional Chinese medicine. We analyzed the reasons why existing high-profile drugs had failed to show clinical benefits and offered our views on the research of traditional herbal medicine for treating TBI.

Comparison of the Antioxidant Activities and Polysaccharide Characterization of Fresh and Dry Dendrobium officinale Kimura et Migo.

It is generally believed that fresh Dendrobium officinale (FDO) has more significant pharmacological activity than dried Dendrobium officinale (DDO); however, the difference has not been clearly shown. Our study compared their antioxidant properties both in vitro and in vivo, and the molecular weight arrangement and monosaccharide composition of the fresh Dendrobium officinale polysaccharides (FDOPs) and the dried Dendrobium officinale polysaccharides (DDOPs) were analyzed by HPLC-GPC and GC-MS. The results showed that the FDO and its polysaccharides had more significant effects on scavenging DPPH, ABTS, and hydroxyl radicals than the DDO. In addition, both the FDO and DDO significantly reduced lipid peroxidation levels and increased the SOD, T-AOC, CAT, and GSH levels in mice with acute liver damage caused by CCl4, while the FDO and its polysaccharides were more effective. Histopathological analysis further verified the protective effect of the Dendrobium polysaccharides on CCl4-induced liver injury. The determination of the polysaccharides revealed that the polysaccharide and mannose contents of the FDO were significantly higher than their dried counterparts, and the homogeneous arrangement of the polysaccharides in the FDO was degraded into three polysaccharide fragments of different molecular weights in the DDO. Overall, our data identified differences in the antioxidant activities of the FDO and DDO, as well as the reasons for these differences.

The cerebral protective effect and mechanism of action of vitamin B6 adjuvant ceftriaxone in experimental pneumococcal meningitis.

BACKGROUND: Pneumococcal meningitis is one of the most common infectious diseases with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 (vitB6) is an important vitamin which acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan through the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status. The aim of this study was to investigate the neuroprotective effect of adjuvant treatment with vitB6 in pneumococcal meningitis. METHODS: The effects of vitB6 on the clinical symptoms, the expression of kynureninase (KYN), Kynurenic acid (KYNA), nicotinamide adenine dinucleotide (NAD) and cytokines in brain tissue and memory of infant Wistar rats subjected to pneumococcal meningitis were researched. At the same time, Kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 was applied in order to further investigate the brain protective effect of vitB6 in bacterial meningitis. RESULTS: Adjuvant therapy of bacterial meningitis with vitB6 could improve the clinical symptoms, learning performance, lead to the maintenance of cellular NAD+ and ATP homeostasis and significantly down-regulate the levels of cytokines in the brain tissue by affecting the KYN pathway. CONCLUSIONS: Adjuvant treatment with vitB6 in pneumococcal meningitis could exert neuroprotective effect via increasing the preservation of cellular energy through affecting the KYN pathway and reducing of the inflammatory response.

Self-healing superamphiphobicity.

Biomimetic self-healing superamphiphobicity is reported on a rough alumina surface with a large number of nanopores that act as nanoreserviors for low surface energy materials that can consecutively release and heal the damaged surface.