The natural carotenoid crocetin has been reported to suppress phenotypes of an experimental myopia model in mice. We investigated the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a −30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage. A concentration of 0.001% of crocetin-containing chow showed a significant (p < 0.001) suppressive effect against both refractive and AL changes in the murine model. Meanwhile, there was no significant difference of AL change between the 0.0003% and the normal chow groups. The concentration of crocetin in the plasma and the eyeballs from mice fed with 0.001% crocetin-containing chow was significantly higher than control and 0.0003% crocetin-containing chow. In conclusion, we suggest 0.001% of crocetin-containing extract is the minimum effective dose showing a significant suppressive effect against both refractive and AL changes in the murine model.
l-Menthol is the main ingredient of peppermint which affects various pharmacological effects such as anti-inflammation and anti-oxidative activity. In this study, we aimed to evaluate the potential effects of l-menthol on cigarette smoke extract (CSE) induced lung injury in rats. Morphology assessment results revealed that administration with l-menthol (5, 10 or 20 mg kg-1 d-1) significantly alleviated CSE-induced lung injury. Besides, l-menthol significantly reduced the inflammatory response by suppressing the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) via downregulating nuclear factor kappa B (NF-κB) and p38 MAPK pathways. Meanwhile, l-menthol decreased the levels of oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase (MPO) whereas it increased the amount of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) through activation of the Nrf2 pathway. Furthermore, the expression of MMP-9 and TIMP-1 in lungs was reduced after treatment with l-menthol, and this indicated that l-menthol might have a potential effect on airway remodeling. Moreover, immunohistochemistry analyses indicated that l-menthol could suppress the infiltration of CD4+ and CD8+ T cells in lung tissues and this was probably due to the immune regulation activity of l-menthol. Taken together, our findings support that l-menthol might be a potential candidate for the treatment of CSE-induced lung injury in rats.
The prevalence of myopia has been steadily increasing for several decades, and this condition can cause extensive medical and economic issues in society. Exposure to violet light (VL), a short wavelength (360-400 nm) of visible light from sunlight, has been suggested as an effective preventive and suppressive treatments for the development and progression of myopia. However, the clinical application of VL remains unclear. In this study, we aimed to investigate the preventive and suppressive effects of VL on myopia progression. Various transmittances of VL (40%, 70%, and 100%) were tested in C57BL/6J mice with lens-induced myopia (LIM). Changes in the refractive error, axial length, and choroid thickness during the 3-week LIM were measured. The myopic shift in refractive error and difference in axial length between the 0 and -30 diopter lens was lessened in a transmission-dependent manner. Choroidal thinning, which was observed in myopic conditions, was suppressed by VL exposure and affected by its transmission. The results suggest that myopia progression can be managed using VL transmittance. Therefore, these factors should be considered for the prevention and treatment of myopia.
1. l-Menthol, as a kind of monocyclic terpene, is widely used in inhalation formulations, food and tobacco. The purpose of this study was to investigate the pharmacokinetic behavior of l-menthol as well as its influence on the activities of cytochrome P450 enzymes.2. The pharmacokinetic behaviors of l-menthol after inhalation (50 mg/kg) and intravenous injection (10 mg/kg) were investigated. A rat liver microsomal model was adopted to elucidate the inhibitory effect of l-menthol on CYP1A2, CYP2C11, CYP2D1/2, CYP2D4, CYP2E1 and CYP3A1 using phenacetin, tolbutamide, omeprazole, dextromethorphan, chlorzoxazone and testosterone as probe drugs, respectively.3. The plasma concentration reached the Cmax within 1.0 h (inhalation) and descended with the T1/2 of 8.53 and 6.69 h for inhalation and i.v. administration, respectively. IC50 for inhibition of l-menthol on CYP 450 enzymes were 4.35 μM for 2D4, 8.67 μM for 1A2, 13.02 μM for 3A1, 14.78 μM for 2D1/2, 234.9 μM for 2C11 and 525.4 μM for 2E1, respectively.4. The results illustrate the pharmacokinetic process of l-menthol in rats and provide information for further rational applications. l-Menthol had moderate inhibitions on CYP2D4 and 1A2, which might affect the disposition of medicines primarily dependent on these pathways.
Objective: Therapeutic results of relapsed/refractory mantle cell lymphoma (R/R MCL) are very disappointing at present, and there is no standard effective treatment regimen. Ibrutinib has been proved to be effective for R/R MCL, however, the sample size of these individual clinical studies was relatively small. Hence, current clinical experience in its usage is still limited. It is necessary to systematically analyze the efficacy and adverse reactions of ibrutinib in the treatment of R/R MCL. Methods: The PubMed, Cochrane Library, and Embase databases were searched using English search terms, mantle cell lymphoma, MCL, and ibrutinib; the VIP, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched using the Chinese search terms, ibrutinib and mantle cell lymphoma. The extracted data were subjected to meta-analysis using R software to deduce the effective rate and occurrence rate of serious adverse reactions. Results: A total of 12 cohort studies were included in this analysis. The results demonstrated that ibrutinib could be an efficient therapy regimen for R/R MCL patients and the effect of combination therapy was better than that of single-drug therapy. During the treatment with ibrutinib, the adverse reactions mainly included hematological toxicity, infection, atrial fibrillation, and bleeding. Discussion: Our analysis showed ibrutinib is an optimal second-line treatment for R/R MCL, and the combination therapy is more effective than monotherapy as it was well-tolerated by the patients. Therefore, the combination of other drugs for R/R MCL should be considered for patients with poor efficacy of ibrutinib alone or relapse after treatment.
Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects.Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects.Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model.Significantly decreased cell viabilities, cell cycle G 1 arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells (p<0.05).And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft (p<0.001).Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis.Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK-and p38-MAPK pathways.Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma.In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues.These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment.
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