Polyphenolic Platform Ameliorated Sanshool for Skin Photoprotection.

Natural evolution has nurtured a series of active molecules that play vital roles in physiological systems, but their further applications have been severely limited by rapid deactivation, short cycle time, and potential toxicity after isolation. For instance, the instability of structures and properties has greatly descended when sanshool is derived from Zanthoxylum xanthoxylum. Herein, natural polyphenols are employed to boost the key properties of sanshool by fabricating a series of nanoparticles (NPs). The intracellular evaluation and in vivo animal model are conducted to demonstrate the decreased photodamage score and skin-fold thickness of prepared NPs, which can be attributed to the better biocompatibility, improved free radical scavenging, down-regulated apoptosis ratios, and reduced DNA double-strand breaks compared to naked sanshool. This work proposes a novel strategy to boost the key properties of naturally occurring active molecules with the assistance of natural polyphenol-based platforms.

[Determination and pharmacokinetics of main components for Psoralea corylifolia-Myristica fragrants drug pair by using UPLC-MS/MS].

To conduct multiple-reaction monitoring(MRM) quantitative analysis with ultra-high performance liquid chromatography coupled with mass spectrometry method(UPLC-MS/MS), determine the concentrations of psoralen, isopsoralen, bakuchiol and dehydrodiisoeugenol in plasma under positive iron mode with chloramghenicol as internal standard, and investigate the pharmacokinetics process of the main components before and after oral administration of drug pair Psoralea corylifolia -Myristica fragrants. Thirty-six SD rats were randomly divided into three group(A, B, C) and received P. corylifolia extract, P. corylifolia-M. fragrants extract, and M. fragrants extract respectively by intragastric administration. The plasma samples were collected at different time points. In the plasma samples, psoralen, isopsoralen, bakuchiol and dehydrodiisoeugenol showed good linear relationship within concentration rages of 0.098 125 to 39.25, 0.084 37 to 33.75, 0.046 875 to 18.75, and 0.11 to 2.2 mg•L⁻¹ respectively. The precision and stability results showed that the determination method of plasma concentration for such compositions was stable and reliable. The pharmacokinetic parameters obtained by DAS 2.0 showed varying differences before and after compatibility. According to the experimental results, the compatibility of P. corylifolia and M. fragrants can significantly impact the pharmacokinetic process of main components, expand their distribution and accelerate their metabolism and elimination in vivo.

Effects of the Tangningtongluo formula as an alternative strategy for diabetics via upregulation of insulin receptor substrate-1.

Tangningtongluo (TNTL), a traditional Chinese medicine, has been widely used in clinics for decades in southwest China. Its pharmacological properties and underlying molecular mechanisms remain unclear. The main goal of ethnopharmacology is to identify novel bioactive compounds derived from plants for use in indigenous medical practice. This knowledge can be used to develop novel pharmaceuticals. In the present study, hyperglycemic C57BL/KsJ­db/db (db/db) mice were used to test the effect of TNTL on microvasculature of the retina and hypoglycemia. Metformin (Met) was selected as a positive control. 26­week­old mice were randomly assigned to receive either the anti­diabetic agent Met [140 mg/kg body weight (BW)], 1.8, 0.9 or 0.45 g/kg BW TNTL, or a placebo. The fasting blood glucose, serum insulin and glycated hemoglobin levels were measured. Histopathologic examination of the pancreas was performed to confirm the hypoglycemic effect. Fluorescein angiography was applied to detect diabetes­induced retinal angioma in the db/db mice. TNTL intake significantly decreased the fasting blood glucose level in a dose­dependent manner. Additionally, TNTL intervention resulted in a significant decrease in the insulin resistance index. Notably, TNTL treatment markedly reduced the speed of retinal degeneration and mildly reversed microvascular caliber degeneration. Western blot analysis indicated that upregulation of phosphorylated insulin receptor substrate­1 (p­IRS­1) by the administration of TNTL may be strongly involved in the improvement of insulin resistance. In conclusion, TNTL exerted a strong hypoglycemic effect and reversed retinal degeneration via upregulation of ISR­1. The present findings provide important scientific evidence supporting TNTL as an effective alternative approach for the management of Type 2 diabetes mellitus.

[Wuwei Wentong Chubi Capsule promotes the autophagy in synovial tissue of adjuvant-induced arthritis rats and its mechanism].

Objective To evaluate the effect of Wuwei Wentong Chubi (WWWTCB) Capsule on the PI3K/AKT/mTOR signaling pathway in the synovial tissues of adjuvant-induced arthritis (AA) rats, and investigate its potential pharmacological mechanisms of treating rheumatoid arthritis. Methods Sixty Sprague Dawley (SD) rats were randomly assigned into six groups evenly: normal group, model group, WWWTCB groups at 0.80, 1.60, 3.20 g/kg body mass, and tripterygium glycosides tablet (TPT) group at 40 mg/kg body mass. Except for the normal group, the other five groups were induced into AA models with Complete Freund's Adjuvant (CFA). The WWWTCB or TPT, was administrated from day 12 after injection of CFA by gavage, once a day for 12 days. After that, unaffected ankle-joint tissues from the AA rats were collected for histopathological examination. The mRNA levels of PI3K, AKT, mTOR, p70s6 and beclin1 in the synovial tissue were detected by real-time quantitative PCR. Meanwhile, the protein levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70s6, p-p70s6 and beclin1 were determined by immunofluorescence histochemical staining and/or Western blotting. Results Compared with the model group, WWWTCB (1.60, 3.20 g/kg body mass) groups showed less ankle-joint injury and decreased proliferation of synovial cells in the ankle-joint tissues. In addition, the administration of WWWTCB decreased the mRNA and protein levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70s6 and p-p70s6, while increased the level of beclin1. Conclusion WWWTCB ameliorated AA in rats. The improvement might be closely related to the inhibitory effect of WWWTCB on the PI3K/AKT/mTOR signaling pathway and its promoting effect on the autophagy activity of synovial cells.

The effects of Qi Teng Xiao Zhuo granules, traditional Chinese medicine, on the expression of genes in chronic glomerulonephritis rats.

BACKGROUND AND AIM: Chronic glomerulonephritis (CGN) is a primary glomerular disease that is related to immune-mediated inflammatory diseases. Qi Teng Xiao Zhuo granules have been proposed as a prescription of traditional Chinese medicine for treatment of CGN, but the comprehensive molecular mechanism underlying this therapeutic effect is not clear to date. The aim of this study was to evaluate and analyze the possible roles and molecular mechanisms of Qi Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats. METHODS: For gene expression analysis, four samples of glomerular tissue from rats in the Qi Teng Xiao Zhuo granule group and four samples each from the adriamycin treated and control groups were hybridized with Agilent Rat 4×44K whole genome microarrays. KEGG and Gene Ontology (GO) analyses and LIMMA, String and Cytoscape software were used to analyze the functional microarray data and screen differentially expressed genes. Hub genes were identified using Pathway Studio software. Real-time PCR was performed to verify the selected genes. RESULTS: Microarray gene expression analysis showed that Pnoc, Cacfd1, Fos, Igll1, Lcn2, and Syk were among the most downregulated genes in the Qi Teng Xiao Zhuo granule group compared with the adriamycin treated group, whereas Cyp2c7, Hsd3b6, Acsm5, and Ugt2b15 were significantly upregulated. Functional analysis demonstrated that metabolism of xenobiotics by cytochrome P450, the B cell receptor signaling pathway, and cytokine-cytokine receptor interaction pathways were significantly downregulated in the Qi Teng Xiao Zhuo granule group and that GO terms related to positive regulation of immune response, immune response-activating signal transduction, cell differentiation, cell cycle, proliferation, and adhesion were significantly affected. Fos and Syk were considered to be potential hub genes. CONCLUSIONS: In the adriamycin-induced CGN rat model, comprehensive molecular mechanisms were involved with complex gene expression alterations containing many altered pathways and GO terms. However, how Qi Teng Xiao Zhuo granules regulate these events warrants further investigation.

[Simultaneous Determination of Seven Chemical Markers and Preliminary Identification of Chemical Constituents in Daodi Psoraleae Fructus-Myristicae Semen Chinese Drug Pair].

OBJECTIVE: To study the simultaneous determination method of daodi Psoraleae Fructus-Myristicae Semen Chinese drug pair for the seven ingredients, and Psoraleae Fructus-Myristicae Semen Chinese drug pair on the chemical composition of initial ownership and identification. METHODS: UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 µm) was used in the determination. The flow rate was kept at 0.25 mL/min, and 2 µL of standard and sample solution were injected in each run. The mobile phase was consisted of acetonitrile and water using a gradient elution. The UPLC/Q-TOF MS condition: Waters HSS T3 (100 mm x 2.1 mm,1.7 µm); capillary voltage 3.0 kV (positive ion mode) and 2.5 kV (negative ion mode); Mass spectrometric detection was carried out on a Waters Xevo G2 Q/ TOF mass spectrometer equipped with an ESI source operating in both positive and negative ion modes. The parameters of the mass spectrometer under the ESI mode were as follows: ion source temperature 110 °C, cone gas flow 50 L/h, desolvation gas temperature 450 °C, desolvation gas flow 800 L/h. RESULTS: The seven chemical markers in the selected linear range had good linearity. The recoveries were in the range of 95.07%-98.16% and RSDs were between 1.23%-1.97%. CONCLUSION: It is suitable for the quality control and further studies of the herb in vivo of daodi Psoraleae Fructus-Myristicae Semen Chinese drug pair.