Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50 of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of Ki=3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.47×10-4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases

Protective Effect of 18 β

Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β-Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP-induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF-α, IL-6, IL-1β, and IFN-γ as well as nuclear translocation of NF-κB. TP also significantly elevated liver MDA and declined hepatic activities of SOD, CAT, and GSH-Px. Assay of TUNEL and apoptosis proteins (Bax, Bcl-2, and active caspase-3) showed that TP induced severe hepatocellular apoptosis. In contrast, low-dose GA (50 mg/kg) significantly reversed TP-induced changes above. However, high-dose GA (100 mg/kg) had no such effect. Overall, these findings indicated that low-dose GA but not high-dose GA exhibited a protective effect against TP-induced hepatotoxicity in rats by anti-inflammation, antioxidation, and antiapoptosis, which suggests that the doses of GA/Licorice should be carefully considered when used together with TWHF or TWHF preparations

Chemical fingerprinting and quantitative analysis of two common Gleditsia sinensis fruits using HPLC-DAD

Gleditsiae Fructus Abnormalis and Gleditsiae Sinensis Fructus are obtained from different developmental stages of fruits from Gleditsia sinensis Lam. (Fam. Leguminosae). The possible interchangeable usage of the two fruits, however, has long been very controversial. Here, high performance liquid chromatography coupled with diode array detection was developed to explore their chemical fingerprinting profiles. Besides, the amounts of aglycons of saponin compounds, echinocystic acid and oleanolic acid in both fruits were quantified. The results indicated that there was no significant difference in the amount of aglycons from the two types of fruits; however, their chromatographic fingerprints showed distinct characteristics. Therefore, the interchangeable application of these fruits has to be taken with a specific precaution

Protective Effect of Pogostone on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis via Inhibition of T Helper Cell

Inflammatory bowel disease (IBD) is a chronic immune-related disease mainly caused by the disequilibrium of T helper (Th) cell paradigm? Pogostone (PO) is one of the major chemical constituents of Pogostemon cablin (Blanco) Benth. The present study aims to investigate the potential benefit of PO against IBD in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis model. PO treatment by enema significantly brought down the disease activity index (DAI) of the TNBS-challenged rats, which was manifested by the ameliorated inflammatory features including ulceration, adhesion, and edema. Hematoxylin-eosin (HE) staining and immunohistochemistry analysis showed that PO effectively relived colon damage by restoring epithelium, and more importantly, by inhibiting the infiltration of pro-inflammatory Th1 and Th17 cells in the colon. Additionally, PO inhibited the activity of myeloperoxidase and secretion of inflammatory cytokines including IFN-γ, IL-12p70, IL-17A, and IL-10. Together with our previous findings, the present data indicated that the anti-IBD effect of PO probably related to its direct inhibition on Th cell proliferation and suppression of the cytokines secretion. These results highlighted the potential of PO as a promising candidate to relieve IBD

Chongcao-Shencha Attenuates Liver and Kidney Injury through Attenuating Oxidative Stress and Inflammatory Response in D-Galactose-Treated Mice

The Chongcao-Shencha (CCSC), a Chinese herbal compound formula, has been widely used as food material and medicine for enhancing physical strength. The present study investigated the possible effect of CCSC in alleviating the liver and kidney injury in D-galactose- (D-gal-) treated mice and the underlying mechanism. Mice were given a subcutaneous injection of D-gal (200 mg/kg) and orally administered CCSC (200, 400, and 800 mg/kg) daily for 8 weeks. Results indicated that CCSC increased the depressed body weight and organ index induced by D-gal, ameliorated the histological deterioration, and decreased the levels of ALT, AST, BUN, and CRE as compared with D-gal group. Furthermore, CCSC not only elevated the activities of antioxidant enzymes SOD, CAT, and GPx but also upregulated the mRNA expression of SOD1, CAT, and GPx1, while decreasing the MDA level in D-gal-treated mice. Results of western blotting analysis showed that CCSC significantly inhibited the upregulation of expression of nuclear factor kappa B (NF-κB) p65, p-p65, p-IκBα, COX2, and iNOS and inhibited the downregulation of IκBα protein expression caused by D-gal. This study demonstrated that CCSC could attenuate the liver and kidney injury in D-gal-treated mice, and the mechanism might be associated with attenuating oxidative stress and inflammatory response

Antioxidative and Anti-Inflammatory Effects of Water Extract of Acrostichum aureum Linn. against Ethanol-Induced Gastric Ulcer in Rats

Acrostichum aureum Linn., a medicinal pteridophyte growing in mangrove forests and coastal regions of tropical and subtropical areas worldwide, has been proved to possess various biological effects. However, the protective effect of Acrostichum aureum Linn. against gastric ulcer still remains unidentified. Therefore, the gastroprotective effect of the water extract of Acrostichum aureum Linn. (WEAC) was investigated in ethanol-induced gastric injury model. According to our results, pretreatment with WEAC (100, 200, and 400 mg/kg) could dramatically decrease the ulcer areas and ameliorate the pathological damage induced by alcohol in rat’s gastric tissues. In addition, WEAC administration prevented the stomach from oxidative damage via markedly increasing the levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and decreasing the malondialdehyde (MDA). Besides, WEAC pretreatment alleviated inflammatory infiltration by reducing the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as decreasing the protein expressions of phosphorylation of IκBα and p65. Taken together, WEAC exerted potential therapeutic efficacy for gastric ulceration, and this may be involved in the suppression of oxidative stress and inflammatory response

Anti-Inflammatory Effects of Heritiera littoralis Fruits on Dextran Sulfate Sodium- (DSS-) Induced Ulcerative Colitis in Mice by Regulating Gut Microbiota and Suppressing NF-κB Pathway

Aim of the Study. This study is aimed at exploring the effects and pharmacological mechanisms of the extracts from the Heritiera littoralis fruit (EFH) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) in mice. Materials and Methods. The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results. LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions. EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway

Gain Measurement of ZnGeP₂ Optical Parametric Oscillator Pulses in a High-Pressure CO₂ Amplifier

Laser pulse amplification by a high-pressure CO2 amplifier in the long-wave infrared (LWIR) spectral range is a feasible technology for strong-field physics research. Crystals such as ZnGeP2 (ZGP) have high nonlinear coefficients and transmittance in the LWIR region, with spectral widths of generated pulses closely matching the gain spectrum of high-pressure CO2 amplifiers. Therefore, ZGP optical parametric oscillation (OPO) may allow higher-efficiency energy extraction in amplifiers, improving the output characteristics of LWIR amplification systems. In this study, the gain measurement of ZGP OPO pulses amplified by a high-pressure CO2 amplifier was carried out for the first time. Single-detector acquisition was utilized to achieve a unified sensor responsivity, and a laser signal-triggered function generator was used to synchronize the seed pulse and amplifier. Six-pass amplification was performed successively, yielding an amplification factor of 4.5 for the peak power and a maximum coefficient of 0.42% cm−1 for the small-signal gain. The gain and loss effect during small-signal amplification were discussed. The potential capability of acquiring ultra-short pulses with ZGP OPO pulses was also explored with the FFT function of MATLAB software