[Research progress on mechanism of Carthamus tinctorius in ischemic stroke therapy].

Carthamus tinctorius is proved potent in treating ischemic stroke. Flavonoids, such as safflower yellow, hydroxysafflor yellow A(HSYA), nicotiflorin, safflower yellow B, and kaempferol-3-O-rutinoside, are the main substance basis of C. tinctorius in the treatment of ischemic stroke, and HSYA is the research hotspot. Current studies have shown that C. tinctorius can prevent and treat ischemic stroke by reducing inflammation, oxidative stress, and endoplasmic reticulum stress, inhibiting neuronal apoptosis and platelet aggregation, as well as increasing blood flow. C. tinctorius can regulate the pathways including nuclear factor(NF)-κB, mitogen-activated protein kinase(MAPK), signal transducer and activator of transcription protein 3(STAT3), and NF-κB/NLR family pyrin domain containing 3(NLRP3), and inhibit the activation of cyclooxygenase-2(COX-2)/prostaglandin D2/D prostanoid receptor pathway to alleviate the inflammatory development during ischemic stroke. Additionally, C. tinctorius can relieve oxidative stress injury by inhibiting oxidation and nitrification, regulating free radicals, and mediating nitric oxide(NO)/inducible nitric oxide synthase(iNOS) signals. Furthermore, mediating the activation of Janus kinase 2(JAK2)/STAT3/suppressor of cytokine signaling 3(SOCS3) signaling pathway and phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase-3ß(GSK3ß) signaling pathway and regulating the release of matrix metalloproteinase(MMP) inhibitor/MMP are main ways that C. tinctorius inhibits neuronal apoptosis. In addition, C. tinctorius exerts the therapeutic effect on ischemic stroke by regulating autophagy and endoplasmic reticulum stress. The present study reviewed the molecular mechanisms of C. tinctorius in the treatment of ischemic stroke to provide references for the clinical application of C. tinctorius.

Rhein activated Fas-induced apoptosis pathway causing cardiotoxicity in vitro and in vivo.

Rhein, one of the main active components of rhubarb (Dahuang) and Polygonum multiflorum (Heshouwu), has a wide range of effective pharmacological effects. Recently, increasing studies have focused on its potential hepatorenal toxicity, but the cardiotoxicity is unknown. In this study, we found that the IC50 of rhein to H9c2 cells at 24 h and 48 h were 94.5 and 45.9µmol/L, respectively, with positive correlation of dose-toxicity and time-toxicity. After the treatment of rhein (106, 124 and 132µmol/L), the number of H9c2 cells decreased significantly, and the morphology of H9c2 cells showed atrophy, round shape and wall detachment. Moreover, the proportion of apoptotic cells in H9c2 cells treated with rhein was significantly increased in a dose-dependent manner. And rhein induced S phase arrest of H9c2 cells and inhibited cell proliferation. Rhein up-regulated ROS, LDH levels and low MMP but down-regulated SOD content in H9c2 cells. Additionally, the results showed that the cardiac function LVEF and LVFS of rhein high-medium-low dose groups (350, 175, 87.5 mg/kg) were significantly reduced. And the contents of Ca2+, cTnT, CK and LDH in serum of KM mice were significantly up-regulated by rhein. Furthermore, western blot results suggested that rhein the above effects via promoting Fas-induced apoptosis pathway in vitro and in vivo. In general, rhein may cause cardiotoxicity via Fas-induced apoptosis pathway in vivo and in vitro, which provides reference for the safe use of medicinal plant containing rhein and its preparations.

Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein.

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo.

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.