To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

IntroductionAcquired resistance to glucocorticoids constitutes a major clinical challenge, often overlooked in the search for compounds to improve the effect of classic steroids. We sought to unravel how a plant-original compound, ginsenoside Rh1, potentiates dexmethasone (DEX)’s potential anti-inflammation properties.MethodsGinsenoside Rh1 combined with DEX was applied in a short-term and long-term treatment protocol for inflammation. Its potential mechanism on anti-inflammation was explored. In addition, the effect of Rh1 on the side-effect induced by DEX was studied. Furthermore, the in vivo anti-inflammatory effects of Rh1 combined with DEX were evaluated in a collagen-induced arthritis (CIA) mice model.ResultsGinsenoside Rh1 potentiates DEX’s anti-inflammatory effects even after prolonged DEX treatment. Rh1 could improve the glucocorticoid receptor (GR)’s transrepression on nuclear factor kappa B (NF-κB) and transactivation on dual specificity protein phosphatase 1 (DUSP1), which is responsible for DEX’s anti-inflammatory effects. Parallel Western blot assay and radioligand binding analysis revealed that Rh1 could increase the expression and binding of GR. This is in sharp contrast to DEX alone, showing a direct link among prolonged treatment, decreasing GR and the abolishment of anti-inflammation. Interestingly, Rh1 does not enhance the transactivation of glucocorticoid-responsive elements (GRE) driven genes - gluconeogenic enzyme glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinasee phosphatase (PEPCK) in primary mouse hepatocytes, a mechanism partly held accountable for the metabolic side-effects. Similar results were found in CIA mice.ConclusionRh1 could potentiate DEX’s anti-inflammatory effects and does not cause a hyperglycemic side effect. Ginsenoside Rh1 combined with DEX may be a promising candidate treatment option for chronic inflammatory diseases in need of long-term immunosuppression therapies.

Melittin, a major component of bee venom, is a water-soluble toxic peptide of which a various biological effects have been identified to be useful in anti-tumor therapy. In addition, Melittin also has anti-parasitic, anti-bacterial, anti-viral, and anti-inflammatory activities. Therefore, it is a very attractive therapeutic candidate for human diseases. However, melittin induces extensive hemolysis, a severe side effect that dampens its future development and clinical application. Thus, studies of melittin derivatives and new drug delivery systems have been conducted to explore approaches for optimizing the efficacy of this compound, while reducing its toxicity. A number of reviews have focused on each side, respectively. In this review, we summarize the research progress on the anti-tumor effects of melittin and its derivatives, and discuss its future potential clinical applications.

Multidrug resistance (MDR) is a major obstacle to chemotherapy in patients with hepatocellular carcinoma (HCC). To overcome MDR and improve chemotherapeutic efficacy, novel reversal agents with higher efficacy and lower toxicity are urgently needed for HCC. The present study was designed to examine the potential reversal activity of bufalin, a toxic ligand isolated from the traditional Chinese medicine 'Chansu' and to elucidate the possible related mechanisms. A multidrug-resistant HCC cell line, BEL-7402/5-FU, was used as the cell model. The working concentration of bufalin as an effective reversal agent, and the cell viability in the reversal experiments were determined by MTT assay. The effects of bufalin at a non-cytotoxic dose on cell cycle distribution, apoptosis and drug efflux pump activity were measured by flow cytometry. Qualitative observation of apoptosis was also carried out by confocal microscopy. Furthermore, the effects of bufalin on the expression of potential genes involved in MDR of BEL-7402/5-FU cells, including thymidylate synthase (TS), P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), B-cell lymphoma-extra large (Bcl-xL) and Bcl-2-associated X protein (Bax), were determined using real-time PCR and western blot analysis. The results showed that bufalin at a concentration of 1 nM enhanced the chemosensitivity of BEL-7402/5-FU cells to 5-FU with a reversal fold of 3.8 which was similar to that of 1 µM verapamil. Bufalin significantly arrested the cell cycle at the G₀/G₁ phase, induced apoptosis through an increase in the Bax/Bcl-xL ratio, inhibited drug efflux pump activity via downregulation of MRP1, and reduced the expression of TS in BEL-7402/5-FU cells. The present study revealed that bufalin effectively reversed MDR in BEL-7402/5-FU cells through multiple pathways. The combination of bufalin with cytotoxic drugs may serve as a promising strategy for the chemotherapy of HCC.

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Body acupuncture was effective in reducing stroke patients' depressive symptoms and had fewer side-effects. It should be considered as an option for neuropsychiatric sequelae of stroke.

BackgroundBufalin is a major active compound of cinobufacini, which comes from dried toad venom and has been used for treatments of various cancers in China for many years. A number of studies have demonstrated that bufalin can induce apoptosis in some cancers. However, effects and mechanism of bufalin on prostate cancer cells remain unknown.MethodsApoptosis assay was measured by the annexin-V/PI flow cytometric assay. Western blot was used to measure Caspase-3 and Bcl-2. qRT-PCR was used to measure the relative expression of miR-181a.ResultsBufalin was found to induce the expression of miR-181a, a small non-coding RNA believed to induce apoptosis by repressing its target gene, BCL-2. In prostate cancer PC-3cell line, bufalin-induced apoptosis can be largely attenuated by a miR-181a inhibitor, which blocked bufalin-induced Bcl-2 reduction and caspase-3 activation.ConclusionsOur dataindicatedthat miR-181a mediates bufalin-induced apoptosis in PC-3 cells. Thus, we presented here a new pharmacological mechanism for bufalin in anti-tumor therapy.

Atorvastatin has been associated with liver injury. We reported here two cases of aminotransferases elevation within 12 h of low-dose atorvastatin therapy. Liver functions were fully recovered to the baseline level 11 days after discontinuation of atorvastatin treatment. The possible relative risk factors included advanced age, chronic and systemic diseases, and coadministration of cytochrome P450 3A (CYP3A) enzyme-dependent metabolic drugs or its inhibitors such as clopidogrel and diltiazem. No significant transaminase elevation was observed after switching to pravastatin. Thus, pravastatin might be safer than atorvastain in patients with chronic or systemic diseases, or with co-administration of CYP3A enzyme-dependent drugs.