Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin.

OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action. METHODS: A human HepG2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability. Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin (mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology. RESULTS: Celastrol decreased the viability of HepG2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in HepG2 cells. Moreover, celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis (up-regulation of cleaved-caspase- 3, -8, -9, and cleaved-PARP) and inhibited the activation of mTOR in vivo. CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR.

2-Hydroxy-3-methylanthraquinone inhibits lung carcinoma cells through modulation of IL-6-induced JAK2/STAT3 pathway.

BACKGROUND: 2-hydroxy-3-methylanthraquinone (HMA), an anthraquinone monomer in traditional Chinese medicine Hedyotis diffusa, has been reported to inhibit the growth of several types of cancer, but its effect on lung cancer has not been adequately investigated. HYPOTHESIS/PURPOSE: This study aimed to test the hypothesis that HMA inhibit the growth, migration, and invasion of lung cancer cells in part via downregulation of interleukin (IL)-6-induced JAK2/STAT3 pathway. METHODS: Growth and apoptosis of lung cancer cells were quantitated by CCK-8 assay and Annexin V-FITC/PI flow cytometric analysis, respectively. Migration and invasion of A549 cells were determined by wound-healing assay and transwell invasion assay, respectively. The effect of HMA on cytokines expression in A549 cells was evaluated by the cytokine antibody array assay. Gene expression and protein levels of related molecular markers were quantitated by real time-PCR and Western blot analysis, respectively. RESULTS: HMA significantly inhibited IL-6-stimulated growth and colony formation of A549 cells, increased the number of apoptotic cells, and inhibited invasion associated with downregulation of expression of IL-6-induced MMP-1, MMP-2, and MMP-9 genes. IL-6 increased the levels of tyrosine phosphorylation of JAK2 and STAT3 in A549 cells, which was reversed by HMA treatment. In addition, HMA reduced the expression of a series of inflammation-related cytokines in A549 cells supernatant, including IL-6, G-CSF, IL-6R, IL-8, MCP-1, RANTES, TNF-α. CONCLUSION: These results suggest that HMA may inhibit the growth and invasion of lung cancer cells in part via downregulation of IL-6-induced JAK2/STAT3 pathway.

Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings.

Here we evaluated the anti-cancer activity of aqueous Oldenlandia diffusa (OD) extracts (ODE) in colorectal cancer (CRC) cells. We showed that ODE exerted potent anti-proliferative, cytotoxic and pro-apoptotic activities against a panel of established CRC lines (HCT-116, DLD-1, HT-29 and Lovo) and primary (patient-derived) human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53. This might be important for p53 activation and subsequent cancer cell apoptosis. Inhibition of AMPK signaling, though dominant negative (dn) mutation or shRNA/siRNA knockdown of AMPKα1 attenuated ODE-exerted CRC cytotoxicity. In vivo, i.p. administration of ODE inhibited HCT-116 xenograft tumor growth in SCID mice. In addition, AMPK activation, mTORC1 inhibition and p53 activation were observed in ODE-treated HCT-116 xenograft tumors. These results suggest that ODE inhibits CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings.

[Effect of xiaoai jiedu recipe on gene expression profiles in H22 tumor-bearing mice].

OBJECTIVE: To explore the mechanism of Xiaoai Jiedu Recipe (XJR) for fighting against tumors by detecting tumor gene expression profiles of H22 tumor-bearing mice. METHODS: H22 tumor-bearing mice were randomly divided into the normal control group, the low dose XJR group, the medium dose XJR group, the high dose XJR group, and the Cisplatin group. The differentially expressed genes of tumor tissues in H22 tumor-bearing mice were detected by using gene chip technique. The antitumor mechanism of XJR associated signaling pathways and gene expressions were found out by pathway analysis. The chemokine signaling pathways were analyzed. RESULTS: XJP could significantly affect multiple signaling pathways associated with tumor growth, apoptosis, and immunity. XJP also could decrease expressions of CCL3 and CXCL2 in the chemokine signaling pathway. CONCLUSION: XJP could inhibit the growth and invasion of tumor cells possibly by affecting expressions of some genes in the chemokine signaling pathway.

[Systems biology is a bridge of integrated traditional Chinese and Western medicine].

The integration of Chinese medicine (CM) and Western medicine (WM) is the only way for the development of medicine, and it is the best form for unifying systems theory and reductionism. In this paper, systems biology and its application in medical research were discussed. The authors put forward that systems biology may possibly interpret the scientific connotation of the complex theoretic systems of CM, which will make WM to well know the human body and disease. We hold that systems biology is a bridge of integrated CM and WM.

Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome.

OBJECTIVE: To investigate the effects of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome induced by mutifactor stimuli. METHODS: SD rats were divided into control, model, Liangxuehuayu Recipe (high, middle and low dose, 18, 9, 4.5 g/kg accordingly). Except the control group, blood stasis model was established in the rest groups. The hemorheological parameters were measured and compared. RESULTS: Blood viscosity at high, moderate and low level in rats with blood stasis significantly increased (P<0.05), but blood viscosity at high level and plasma viscosity was significantly decreased in rats induced by some stimuli after Liangxuehuayu Recipe were intra-gastrically administered for 1 weeks (P<0.01, P<0.05). CONCLUSIONS: Liangxuehuayu Recipe is effective in improving hemorheology, and has important application value in the prevention of occurrence and development of ischemic stroke.

[The establishment of research inherit mode of famous academic thoughts].

To study and summarize the academic thoughts of famous Chinese medicine doctors is the main pathway of developing Chinese medicine theories. It is of important significance in enriching and developing the Chinese medicine theories by combining traditional and modern research methods, merging multiple disciples to study the research inherit mode of famous academic thoughts. The major study links include: (1) To refine scientific hypotheses from huge amount of clinical case records; (2) To find the literature sources; (3) To embody the practice significance of the innovative theories by clinical studies; (4) To reveal the scientific connotation of Chinese medicine theories by experimental studies. We hope to reach the goal of innovating and developing Chinese medicine theories on the basis of inheritance by integrating clinical case records, tracing the literature sources, clinical and experimental studies.

[Viewing from the toll-like receptor/nuclear factor-kappaB signaling pathway to explore the immunomodulatory mechanism of Chinese drugs].

Many Chinese drugs (CHD) have showed their significant effects of integral immune-regulation, and lots of researches have conducted in recent years for exploring their mechanism from different levels, like cytological, molecular and genetic levels. In this paper, the relation between immune-regulation of CHD and Toll-like receptors/nuclear factor-kappaB (TLRs/NF-kappaB) signaling pathway was introduced in brief based upon the achievements of previous researches. It was pointed out that the two are closely related, to explore mechanism of CHD in this way is meaningful not only for further deepening the theoretical understanding of CHD's pharmacological immunoregulation, but also be practically facilitate for enhancing therapeutic efficacy of CHD and developing new CHD.

[Effects of Liangxue Tongyu Formula on brain edema and expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rats with intracerebral hemorrhage].

OBJECTIVE: To investigate the effects of Liangxue Tongyu Formula (LXTYF), a compound traditional Chinese herbal medicine, on brain edema in rats with intracerebral hemorrhage and to explore the mechanism. METHODS: Intracerebral hemorrhage was induced by using the intrastriatal autologous blood injection. Rats were randomized into sham-operated (SO) group, intracerebral hemorrhage (ICH) group and LXTYF group. Rats in the LXTYF group were intragastrically administered with LXTYF every day while the other two groups were given normal saline. Brain water content was determined at 24, 48, 72, and 120 h after intracerebral hemorrhage. Matrix metalloproteinase-9 (MMP-9) level, and MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expressions in perihematoma area were detected by gelatin zymography and fluorescence quantitative real-time polymerase chain reaction at the four time points, respectively. RESULTS: Water content in the ICH group was highly elevated after intracerebral hemorrhage, and reached to the peak at 72 h. Compared with the ICH group, the LXTYF group had lower water contents at 48, 72 and 120 h after intracerebral hemorrhage (P<0.01). The difference in water content between the LXTYF and SO groups was significant only at 72 h (P<0.01). Although the pro-MMP-9 level and MMP-9 activity in the LXTYF and ICH groups were enhanced, they were still lower in the LXTYF group than in the ICH group (P<0.01 for 24, 48, 72 and 120 h, respectively). And there was no significant difference in them between the LXTYF group and the SO group at 120 h. Meanwhile, MMP-9 mRNA expressions were increased in the ICH and LXTYF groups, but the levels in the LXTYF group were significantly lower (P<0.01 for 48, 72 and 120 h, respectively) than those in the ICH group. Also, TIMP-1 mRNA expressions at 24, 48, 72 and 120 h after intracerebral hemorrhage were up-regulated in the LXTYF group, and there were significant differences in TIMP-1 expressions between the LXTYF group and ICH group after intracerebral hemorrhage (P<0.01). CONCLUSION: Liangxue Tongyu Formula ameliorates brain edema in rats after intracerebral hemorrhage by inhibiting MMP-9 expression and activity and up-regulating TIMP-1.

[Clinical study on aitongping capsule in treating cancerous pain].

OBJECTIVE: To explore the therapeutic effect and mechanism of Aitongping capsule (ATP) in treating cancerous pain. METHODS: Sixty cancer patients were randomly divided into two groups, 30 patients in the treated group took ATP and 30 patients in the control group took diclofenac, 1 week of treatment was applied. The relevant clinical conditions of cancerous pain, the content of plasma beta-endorphin (beta-EP) and c-AMP, hemorheological index, improuement of life quality of patients, occurrence rate of adverse reaction were observed before and after treatment. RESULTS: The total effective rate in the treated group and in the control group was 90.0 % and 83.3%, respectively, difference between them showed no significance. However, there were significant difference between the two groups in such aspects as the degree of pain relieving, the decrease of pain episodes, the shortening persistent time of pain and the initiation time of analgesic action and prolonged analgesic duration, the decrease of tenderness and percussion pain, the increase of plasma beta-EP content and the decrease of cAMP (P< 0.05 or P< 0.01). The evidences also showed that it was better in improving quality of life, ameliorating hemorheologic indexes and reducing incidence of adverse reaction in the treated group than in the control group (P <0.05 or P <0.01). CONCLUSION: ATP has affirmative effect on cancerous pain, its analgesic effect may be associated with the increasing of plasma beta-EP content, decreasing of cAMP level and ameliorating of hemorheologic indexes.