ABSTRACT
Andrographolide， a diterpene lactone， is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata （Burm.f.）Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation， bacteriostat， anti-virus， anti-tumor， protecting liver， promoting the function of gallbladder， and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific， it can inhibit nuclear factor-κB （NF-κB）， signal transduction and activator of transcription 3 （STAT3）， and other signaling pathways， reduce the synthesis and release of downstream inflammatory mediators， and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time， it suppresses a variety of tumor cells by inhibiting tumor cell proliferation， blocking cell cycle， and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， NF-κB， and secreted glycoprotein/β-catenin （Wnt/β-catenin）. In addition， it can also alleviate diabetes by regulating glucose metabolism. According to related research， it often exerts pharmacological effects through multiple pathways and multiple targets， but the specific targets are unclear. Therefore， this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions， which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.
ABSTRACT
The incidence and mortality of cancer are increasing year by year， seriously threatening human health. At present， the chemotherapy-based treatment of cancer can prolong the survival time of patients， but its severe side effects and adverse reactions often lead to poor prognosis. Therefore， searching for anti-cancer drugs with high efficiency and low toxicity has become the focus of clinical attention from all over the world. The effective components of Chinese medicine have the advantages of mild side effect and multi-target regulation， and their anti-tumor activities are highly favored by many researchers. Shikonin， a naphthoquinone compound， is the main effective component of Arnebiae Radix， with anti-tumor， anti-inflammatory， antioxidant， and other pharmacological effect. Studies have shown that shikonin possesses significant anti-tumor activities against a variety of tumor cells， and it can inhibit the development of many cancers， such as breast cancer， lung cancer， liver cancer， cervical cancer， ovarian cancer， colon cancer， and prostate cancer. The anti-tumor mechanism of shikonin is mainly related to multi-pathway and multi-target inhibition of tumor cell proliferation， the promotion of reactive oxygen species （ROS） production， induction of tumor cell apoptosis， cell cycle arrest， and tumor cell autophagy， and the inhibition of tumor cell migration and invasion. In addition， shikonin can increase the sensitivity of tumor cells to anti-tumor drugs and reverse the drug resistance of tumor cells. The signaling pathways involved in the anti-tumor effect of shikonin include phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， PI3K/Akt/mammalian target of rapamycin （mTOR）， mitogen-activated protein kinase （MAPK）， pyruvate kinase M2/signal transducer and activator of transcription protein 3 （PKM2/STAT3）， and Kelch-like epichlorohydrin-related protein 1/nuclear factor E2-related factor 2 （Keap1/Nrf2）. The anti-tumor effects are mainly achieved through the regulation of the PI3K/Akt signaling pathway. Based on the relevant literature on the anti-tumor effect and mechanism of shikonin in China and abroad， the present study reviewed the research progress in the past three years to provide useful references for the further study of the anti-tumor effect of shikonin and the research and development of new antineoplastic drugs.
ABSTRACT
Objective:To investigate the effect of<italic> Stemona tuberosa</italic> alkaloids on the apoptosis of human hepatoma SMMC-7721 cells and the expression of apoptosis-related proteins including B lymphocytoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）. Method:SMMC-7721 cells were routinely cultured， passaged， and treated with various concentrations （50， 75， 112， 167， and 250 mg·L<sup>-1</sup>） of <italic>S. tuberosa </italic>alkaloids， while those in the blank control group were only treated with 10% fetal bovine serum. The cell proliferation was determined by tetrazolium bromide （MTT） colorimetry and colony assay and the cell apoptosis by Hoechst 33258 staining. The protein expression levels of Bcl-2， Bax， and cleaved Caspase-3 were detected by Western blot. Result:<italic>S. tuberosa</italic> alkaloids inhibited the proliferation of SMMC-7721 cells， and the inhibition rate was significantly increased in comparison with that in the blank control group （<italic>P</italic><0.01）， with the half maximal inhibitory concentrations （IC<sub>50</sub>） at 24 h， 48 h， and 72 h being （173.36±8.75）， （112.14±16.50）， and （96.41±2.60）mg·L<sup>-1</sup>， respectively. The cell colony-inhibitory activity was significantly increased in a dose-dependent manner （<italic>P</italic><0.01）. Compared with the blank control group， <italic>S. tuberosa</italic> alkaloids promoted the apoptosis of SMMC-7721 cells， manifested as increased number of apoptotic cells and elevated apoptotic rate （<italic>P</italic><0.01）. The typical morphological changes such as brightly blue-fluorescent condensed nuclei， cytoplasmic shrinking， and karyopyknosis were found under the upright fluorescence microscope. As revealed by comparison with the blank control group， the expression of Bcl-2 was significantly down-regulated （<italic>P</italic><0.01）， while the protein expression levels of pro-apoptotic protein Bax and cleaved Caspase-3 in the 75， 112， 167， and 250 mg·L<sup>-1</sup> <italic>S. tuberosa</italic> alkaloids groups were significantly up-regulated （<italic>P</italic><0.01）. Conclusion:<italic>S. tuberosa </italic>alkaloids inhibit the proliferation of SMMC-7721 cells and promote their apoptosis possibly by inhibiting Bcl-2 protein expression and promoting Bax and cleaved Caspase-3 protein expression.
ABSTRACT
Polydatin， a polyphenolic compound， is the main active component of Chinese medicine Polygoni Cuspidati Rhizoma et Radix and has a variety of pharmacological activities. In recent years， there are more studies on the pharmacological effects and mechanisms of polydatin. Modern pharmacological studies show that polydatin has protective effects on the nervous system， cardio-cerebral vascular system， and respiratory system， and also has significant effects on the liver， kidney， lung， and other organs. Its effect of regulating blood glucose and blood lipid on atherosclerosis is significant， and the anti-fibrosis effect is significant on the liver and kidney. Polydatin can inhibit many types of tumor cells， suppress proliferation and induce apoptosis of tumor cells. Polydatin can also resist inflammation and radiation， protect bone marrow， and promote wound healing. Based on the literature on the pharmacological effects of polydatin， the authors found that the single pharmacological mechanism of polydatin is often regulated by multi-target proteins and multiple pathways， but the most of action targets are unclear， which needs to be further investigated. This study summarized the research progress on the pharmacological action and mechanism of polydatin in the past five years and put forward some suggestions on its present research situation and future research direction to broaden the research ideas of researchers and speed up the identification of the targets of its pharmacological effect. This study is expected to provide a scientific theoretical basis for the further development and utilization of polydatin.