Recent Progress in Metal-Catalyzed Selective Oxidation of 5-Hydroxymethylfurfural into Furan-Based Value-Added Chemicals.

5-hydroxymethylfurfural (HMF), one of the most significant biomass-derived renewable resources, has been widely utilized to create furan-based value-added chemicals such as 2,5-diformylfuran (DFF), 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), 5-formyl-2-furancarboxylic acid (FFCA), and 2,5-furan dicarboxylic acid (FDCA). Indeed, DFF, HMFCA and FFCA are key intermediate products during the oxidation of HMF to FDCA. Herein, this review aims to demonstrate the recent advances in metal-catalyzed oxidation of HMF into FDCA via two different reaction routes (HMF-DFF-FFCA-FDCA and HMF-HMFCA-FFCA-FDCA). All the four furan-based compounds are comprehensively discussed by the selective oxidation of HMF. Additionally, various metal catalysts, reaction conditions, and reaction mechanisms used to obtain the four different products are systematically reviewed. It is anticipated that this review will provide related researchers with new perspectives and speed up the development of this field.

[Study on intervention effect of Astragali Radix-Curcumae Rhizoma on growth and metastasis of colon cancer in orthotopic transplantation mice model of colon cancer].

Astragali Radix-Curcumae Rhizoma is a classic drug pair mainly used for the treatment of digestive tract-related inflammation and tumors, but the ratio is not fixed in clinical practice. In order to study whether the anti-tumor effect of the drug pair is diffe-rent under different ratios, orthotopic transplantation model of colon cancer was established in mice. Then the principal component analysis(PCA) and cluster analysis(CA) were used to explore the effect of different ratios of the drug pair on the tumor growth and metastasis, and select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. After administration for 15 days, the body weight of colon cancer mice with the tumor removed, the tumor volume and the number of liver metastases were mea-sured; the pathological changes of tumor tissue and liver tissue were observed by HE staining. At the same time, Western blot method was used to detect the protein expression level of tumor growth-related indicators in tumor tissue(Ki67, HBP1, AFP) and tumor metastasis-related indicators in liver tissue(ß-catenin, E-cadherin, vimentin, p53) of the tumor-bearing mice. Subsequently, PCA and CA were used to select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. The experimental results showed that different ratios of Astragali Radix-Curcumae Rhizoma inhibited tumor growth and metastasis to varying degrees. The ratio at 1∶1 of Astragali Radix-Curcumae Rhizoma had the best inhibitory effect on tumor growth, and the 2∶1 ratio group had the best effect on inhibiting liver metastasis and improving weighed loss. Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of HBP1 in tumor tissue of colon cancer mice, and significantly down-regulated the protein expression of Ki67 and AFP in tumor tissue; meanwhile, Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of E-cadherin in liver tissue of colon cancer mice, and significantly reduced the protein expression of ß-catenin, vimentin and p53 in liver tissue. PCA results showed that the first three groups in the Astragali Radix-Curcumae Rhizoma compatibility group that were closer to the sham operation group were in the order of 2∶1, 1∶1 and 3∶2, among which the center distance of the 2∶1 group was the shortest from the sham operation group, indicating that the ratio 2∶1 of Astragali Radix-Curcumae Rhizoma had the best intervention effect on colon cancer in mice, consistent with the commonly used clinical proportion. CA results showed that 11 groups of colon cancer mice were classified into 3 categories: Astragali Radix-Curcumae Rhizoma compatibility group, sham operation group and model group, which was consistent with the theory. The results of this study provide a basis for more effective clinical application of Astragali Radix-Curcumae Rhizoma in the treatment of colon cancer, and provide new ideas for the development of classic drug pairs.

[Mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on intervention of cerebral ischemia based on network pharmacology-molecular docking].

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.

[Effect and mechanism of aerial parts of Salvia miltiorrhiza effective constituents on glycolipid metabolism of high sugar-induced Drosophila melanogaster metabolic disorder model].

To evaluate the effect and mechanism of aerial parts of Salvia miltiorrhiza(SM) on high sugar-induced Drosophila melanogaster metabolic disorder model. The levels of glucose, triglyceride and protein in SM were detected; nymphosis time was recorded, and the reliability of metabolic disorder model as well as the mechanism of aerial parts of SM were evaluated based on metabonomics. The results showed that the levels of glucose and triglyceride in model group were significantly higher than those in normal control group(P<0.05). As compared with the model group, the glucose level was significantly decreased in gliclazide(GLZ) group, SM medium(SM-M) and high(SM-H) dose groups(P<0.05, P<0.01); the triglyceride level was significantly decreased in GLZ group and SM-H group(P<0.05, P<0.01). By principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), the metabolic level of model ones was recovered to a certain degree after intervention by aerial parts of SM. Seventeen marker compounds and four major metabolic pathways were obtained by screening differential metabolites, comparing literature and retrieving the database. The aerial parts of SM may regulate glycolipid metabolism through the impact on histidine metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, cysteine and methionine metabolism and glycerolipid metabolism. Extract from aerial parts of SM can regulate the glycolipid metabolism of D. melanogaster metabolic disorder model and make it return to normal condition. This paper provides reference for the value discovery and resource utilization of the aerial parts of S. miltiorrhiza.

Beneficial Effects of a Flavonoid Fraction of Herba Epimedii on Bone Metabolism in Ovariectomized Rats.

A flavonoid fraction of Herba Epimedii, including eight flavonoid glycoside compounds, epimedoside A, ikarisoside F, baohuoside II, sagittatoside A, sagittatoside B, 7-O-rhamnosyl icariside II, 2"-O-rhamnosyl icariside II, and baohuoside I, was isolated and prepared from the leaves of Herba Epimedii. This study was conducted to assess the potential effect of the flavonoid fraction of Herba Epimedii on osteoporosis in ovariectomized rats. Rats received repeated administration of a vehicle (ovariectomized), the flavonoid fraction of Herba Epimedii (7.5, 15, 30 mg/kg/d), and ipriflavone (200 mg/kg/d) once a day for 8 weeks, beginning 4 weeks after ovariectomization. Then, the bone turnover markers, bone biomechanical properties, trabecular architecture, and related protein expressions were evaluated by biochemical assay kits, mechanical testing, microcomputed tomography, immunohistochemical evaluation, and Western blot analysis. Treatment with the flavonoid fraction of Herba Epimedii (15, 30 mg/kg/d) and ipriflavone (200 mg/kg/d) significantly increased bone strength while dramatically inhibiting the serum alkaline phosphatase and tartrate-resistant acid phosphatase levels in ovariectomized rats. Furthermore, the flavonoid fraction of Herba Epimedii also increased osteoprotegerin protein expression and reduced the receptor activator of nuclear factor-κB ligand protein expression compared with ovariectomized rats. In addition, the microcomputed tomography results showed that the flavonoid fraction of Herba Epimedii treatment significantly improved trabecular bone mineral density and restored the bone microarchitecture in ovariectomized rats. Therefore, our results indicated that the flavonoid fraction of Herba Epimedii might be beneficial for improving postmenopausal osteoporosis and should be considered as a promising candidate for treating postmenopausal osteoporosis.

[Evaluation of nephrotoxicity induced by total terpenoids from Alismatis Rhizoma on HK-2 cells in vitro and its induction of apoptosis].

To evaluate the nephrotoxicity of total terpenoids from Alismatis Rhizoma on human kidney proximal tubular cells (HK-2), explore the iraction in inducing apoptosis of HK-2 cells, and provide reference for the research of controversial nephrotoxicity of total terpenoids from Alismatis Rhizoma, HK-2 cells were used and cells viability was measured by MTT colorimetric method. An assessment of cells apoptosis was also conducted by using flow cytometry. Meanwhile western blot assay was used to detect the protein expressions of caspase-3, Bcl-2, Bcl-xl, Kim-1, clusterin and TFF-3. At last, q-PCR was used to detect the mRNA expressions of caspase-3, Bcl-2, Bcl-xl, Kim-1, clusterin and TFF-3. The flow cytometry results showed that cells apoptosis rate was (37.48±1.76)%, (26.91±1.91)% and (25.61±2.05)% respectively after treating with total terpenoids (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹). Western blot results showed that Bcl-2 and Bcl-xl protein levels were significantly decreased after treating with total terpenoids (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹), while the protein expression of caspase-3 was significantly increased. q-PCR results were the same with western blot results, that mRNA expressions of Bcl-2 and Bcl-xl were significantly decreased while mRNA expression of caspase-3 was significantly increased after treating with total terpenoids (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹). Western blot results and q-PCR results showed that both mRNA and protein expressions of Kim-1, clusterin and TFF-3 were significantly increased after treating with total terpenoids from Alismatis Rhizoma (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹). HK-2 cells in vitro evaluation results showed that, total terpenoids from Alismatis Rhizoma may have nephrotoxicity effect, but further study is still needed for verification; meanwhile, they could induce HK-2 cells apoptosis, providing basis for nephrotoxicity study and safe application of Alismatis Rhizoma.

[Evaluation analysis of alkaloids in seed of Sophora flavescens from Shanxi province and exploration of its utilization value].

According to the research strategy of resource chemistry of Chinese medicinal materials and Chinese medicinal resources recycling utilization, this study intends to explore the potential resource-oriented utilization value of the seed of Sophora flavescens by contrasting with its kindred plant S. alopecuroides. This study established a rapid UPLC-Q-TOF-MS/MS and UPLC-TQ-MS/MS method to determine the alkaloids in the seed of S. flavescens. Results of UPLC-Q-TOF-MS/MS analysis showed that the alkaloids in the seed of S. flavescens were highly similar with S. alopecuroides.In the determination of 7 kinds of alkaloids, the total content was 11.203 and 15.506 mg•g⁻¹ in the seed of S. flavescens and S. alopecuroides, respectively. The content of oxymatrine, oxysophocarpine and sophoridine is high in the seed of S. flavescens. The results indicated that the seeds of S. flavescens. could be an important material resource to obtain alkaloids.

Development of innovative structural components of Chinese medicine by multidisciplinary crossing.

"Prescription embodied in Preparation", Chinese medicine preparation, aims to study the specific form of Chinese medicine from raw materials to preparation for acting on patients directly. Its development has gone through three stages according to the characteristics of raw materials pretreatment, including "direct smash and initial extraction for Chinese materia medica", "Extensive extraction and preliminarily impurity for Chinese materia medica" and "Refining and purification for Chinese materia medica". With the development of new technologies and new theories, Chinese medicine preparation emerged in a new stage: structural components of Chinese medicine, with the characteristics of definited material basis, clear mechanisms, determined ADME/T properties, reasonable drug release system designs and scientific productions quality controls. This requires multidisciplinary to solve systemly the problems of Chinese medicine preparation. In this article, we reviewed the development of Chinese medicine preparation in different times, and analyzed the development and the characteristics of Chinese medicine preparation; and mainly focused on a fact that multidisciplinary promoted the study and development of Chinese medicine preparation, especially in structural components of Chinese medicine. It provides development direction and theoretical basis for Chinese medicine preparation.

[Effect of different composition structures of total paeony glycoside component and total phenolic acid component of Chuanxiong Rhizome on human umbilical vein endothelial cells with hypoxic injury].

OBJECTIVE: To study the effect of different composition structures of total paeony glycoside (TPG) component and total phenolic acid of Ligusticum chuanxiong ( TLPA) on sodium dithionite (Na2S2O4) -induced human umbilical vein endothelial cells (HUVEC) hypoxic injury. The baseline geometric proportion was used to design different components structure. And then the best structure of components by cell injury model were optimized. METHOD: A HUVEC hypoxic injury model was established by being induced of Na2S2O4. Cell viability was measured by MTI colorimetric method, intracellular superoxide dismutase (SOD) activity, malondialdehyde (MDA), lactate dehydrogenase( LDH) levels, nitric oxide (NO) contents were measured by kits. At last, Western blot analysis was used to detect the expression of two proteins, Bcl-2 and Bax. RESULT: Compared with the model group, TPG component, TLPA component at different composition structures can significantly increase SOD activity and decrease MDA, LDH, NO levels (P < 0.01, P < 0.05). Paeoniae Radix Rubra and Chuanxiong Rhizoma components can downregulate the expression of Bax protein and upregulate the expression of Bcl-2 protein. The ratio of Bcl-2 and Bax was significantly increased (P < 0 01, P < 0 05), it means that cell apoptosis was inhibited. The results indicate that among all the component composition structures, TPG and TLPA component at the proportion of 8: 2 had the best protection on hypoxic injury of endothelial cells. CONCLUSION: TPG component and TLPA component can resist HUVEC hypoxia injury, the protective effect was the most evident under the structure of 8: 2, which may be due to the inhibition of intracellular lipid peroxidation and cell apoptosis.

[Structural components of Chinese medicine and pharmacology network: systematical overall regulation on pathological network].

Development of the disease is the result of several factors involved in biological network changes. The nature of drug intervention is to regulate these pathological changes to the normal range. Advantages of traditional Chinese medicine (TCM) are to integrally and systematically regulate this biological networks and systematic pathology through multi-targets, multi-levels, multi-channels. Structural components TCM provides the controlled and precise basis "substance" for this regulation and also to clarify the "truth" of the nature of the regulation by the network pharmacology. Network pharmacology provides new strategy for the research on mechanism of structural components TCM. This study not only reflects the overall characteristics of the development of the disease, but also fully embodies the essence of TCM for preventing and treating diseases through changing traditional model on "one drug, one gene, one disease". This paper explores systematically the integration essence, features and research strategies of structural components TCM and the network pharmacology, understand the interaction of structural components TCM and body from the perspective of the overall concept of improving or restoring the balance of.biological networks. It is effective measure to reveal the structure of a multi-component for regulating biological networks mechanisms, and also provide new ideas and methods for further scientific research and innovation of structural component TCM.

[Research development of the chemical material basis of Alisma orientalis and its toxicity].

Alisma orientalis is a traditional herb medicine commonly used in clinical. With the increasing report of its toxicity in clinical, the renal toxicity of Alisma orientalis has got gradually attention. This paper systematically reviews the research on the chemical material basis of Alisma orientalis including its chemical composition and toxicity of ingredients; and also declares its toxic ingredients and targets according to Network toxicology. Based on the controversy on renal toxicity of Alisma orientalis, we analyzed the possible reasons that may be associated with renal toxicity. It might be associated with the differences of the material basis composition and regulatory toxicology network, differences in employed processing technology, the metabolic function leading to accumulation of compounds, dosage and duration of the experiment and compatibility. The review provides possible reference and ideas for the quality control and rational use of Alisma orientalis.

Hederagenin from the leaves of ivy (Hedera helix L.) induces apoptosis in human LoVo colon cells through the mitochondrial pathway.

BACKGROUND: Colorectal cancer has become one of the leading cause of cancer morbidity and mortality throughout world. Hederagenin, a derivative of oleanolic acid isolated from the leaves of ivy (Hedera helix L.), has been shown to have potential anti-tumor activity. The study was conducted to evaluate whether hederagenin could induce apoptosis of human colon cancer LoVo cells and explore the possible mechanism. METHODS: MTT assay was used for evaluating cell viability while Annexin V-FITC/PI assay and Hoechst 33342 nuclear stainining were used for the determination of apoptosis and mitochondrial membrane potential. DCFH-DA fluorescence staining and flow cytometry were used to measure ROS generation. Real-time PCR and western blot analysis were performed for apoptosis-related protein expressions. RESULTS: MTT assay showed that hederagenin could significantly inhibit the viability of LoVo cells in a concentration-dependent and time-dependent manner by IC50 of 1.39 µM at 24 h and 1.17 µM at 48 h. The apoptosis ratio was significantly increased to 32.46% and 81.78% by the induction of hederagenin (1 and 2 µM) in Annexin V-FITC/PI assay. Hederagenin could also induce the nuclear changes characteristic of apoptosis by Hoechst 33342 nuclear stainining under fluorescence microscopy. DCFH-DA fluorescence staining and flow cytometry showed that hederagenin could increase significantly ROS generation in LoVo cells. Real-time PCR showed that hederagenin induced the up-regulation of Bax and down-regulation of Bcl-2, Bcl-xL and Survivin. Western blotting analysis showed that hederagenin decreased the expressions of apoptosis-associated proteins Bcl-2, procaspase-9, procaspase-3, and polyADP- ribosepolymerase (PARP) were increased, while the expressions of Bax, caspase-3, caspase-9 were increased. However, there was no significant change on caspase-8. CONCLUSIONS: These results indicated that the disruption of mitochondrial membrane potential might contribute to the apoptosis of hederagenin in LoVo cells. Our findings suggested that hederagenin might be a promising therapeutic candidate for human colon cancer.

[New exploration on effect of characteristics of traditional Chinese medicine components structure on multi-ingredient/component pharmacokinetics].

The study on the pharmacokinetics of traditional Chinese medicines (TCMs) is a linking science during the modernization of TCMs, and plays an important role in the studies on the complex material base of TCMs, the in vivo process of ingredient/ component and the pharmacokinetics-pharmacodynamics correlation. However, because of the multi-ingredient/component system of TCMs, how to scientifically reveal the pharmacokinetics that is consistent with TCMs' characteristics has long been a hotspot and difficulty for the exploration. The optimal composition structure of the material basis of TCMs shows the best efficacy, while the difference between the multi-ingredient/component composition structures in the efficacy is closely related to their absorption, transport, metabolism and excretion in vivo. In this article, the authors systematically review the study methods for pharmacokinetics of TCMs and their compounds, and explore the pharmacokinetics of TCMs based on the "component structure theory". As a result, the method for integrating TCM component structure and the TCM pharmacokinetics was proposed to be adopted to intensively study the effect of the component structure on the in vivo TCM multi-ingredient/component pharmacokinetic characteristics, in order to promote the TCM modernization and innovation in China.

[Technical scheme of real-time evaluation of traditional Chinese medicine orally disintegrating tablets].

Orally disintegrating tablets (ODT), a kind of new solid tablet that rapidly disintegrates to work in the mouth, has became the hot form of new drug research in recent years with many advantages, such as the convenient taking, a widely applicable people, fast acting, high bioavailability, good compliance, and so on. ODT has been widely used in chemical medicines, while the application of it in traditional Chinese medicines (TCMs) is still in the stage of development The development of TCMs ODT provides a new direction for the research of Chinese medicine new dosage, accelerates the pace of connecting to the world and modernization of Chinese medicine. This dosage has a broad market prospect, and its quality control and assessment standards, taste, the disintegration time in vitro and evaluation method are the key factors that affect the industrialization, standardization of Chinese medicine ODT. Therefore, this paper reviewed the characteristics, preparation, taste masking technology and quality evaluation with new technology of ODT. Meantime, numerous application examples of ODT used in traditional Chinese medicine were described. We expect to provide the reference and utilization for the development of traditional Chinese medicine orally disinteeratine tablets.

[Establishment of industry promotion technology system in Chinese medicine secondary exploitation based on "component structure theory"].

The purpose of the secondary exploitation of Chinese medicine is to improve the quality of Chinese medicine products, enhance core competitiveness, for better use in clinical practice, and more effectively solve the patient suffering. Herbs, extraction, separation, refreshing, preparation and quality control are all involved in the industry promotion of Chinese medicine secondary exploitation of industrial production. The Chinese medicine quality improvement and industry promotion could be realized with the whole process of process optimization, quality control, overall processes improvement. Based on the "component structure theory", "multi-dimensional structure & process dynamic quality control system" and systematic and holistic character of Chinese medicine, impacts of whole process were discussed. Technology systems of Chinese medicine industry promotion was built to provide theoretical basis for improving the quality and efficacy of the secondary development of traditional Chinese medicine products.

[Establishment of prescription research technology system in Chinese medicine secondary exploitation based on "component structure" theory].

Chinese medicine prescriptions are the wisdom outcomes of traditional Chinese medicine (TCM) clinical treatment determinations which based on differentiation of symptoms and signs. Chinese medicine prescriptions are also the basis of secondary exploitation of TCM. The study on prescription helps to understand the material basis of its efficacy, pharmacological mechanism, which is an important guarantee for the modernization of traditional Chinese medicine. Currently, there is not yet dissertation n the method and technology system of basic research on the prescription of Chinese medicine. This paper focuses on how to build an effective system of prescription research technology. Based on "component structure" theory, a technology system contained four-step method that "prescription analysis, the material basis screening, the material basis of analysis and optimization and verify" was proposed. The technology system analyzes the material basis of the three levels such as Chinese medicine pieces, constituents and the compounds which could respect the overall efficacy of Chinese medicine. Ideas of prescription optimization, remodeling are introduced into the system. The technology system is the combination of the existing research and associates with new techniques and methods, which used for explore the research thought suitable for material basis research and prescription remodeling. The system provides a reference for the secondary development of traditional Chinese medicine, and industrial upgrading.

Research progress on the effect of pyroptosis on the occurrence, development, invasion and metastasis of colorectal cancer.

Pyroptosis is a type of programmed cell death mediated by gasdermines (GSDMs). The N-terminal domain of GSDMs forms pores in the plasma membrane, causing cell membrane rupture and the release of cell contents, leading to an inflammatory response and mediating pyrodeath. Pyroptosis plays an important role in inflammatory diseases and malignant tumors. With the further study of pyroptosis, an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence, development, treatment and prognosis of colorectal cancer. This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence, development, treatment and prognosis of colorectal cancer (CRC) and to provide ideas for the clinical diagnosis and treatment of CRC.

Antioxidative and anti-inflammatory activities of paeoniflorin and oxypaeoniflora on AGEs-induced mesangial cell damage.

Paeonia suffruticosa, an important traditional herbal medicine, has been reported to prevent the pathogenesis of diabetic nephropathy through modulating advanced glycation end products-induced inflammatory and oxidative stress responses. However, little was known about the protective effect of the two major compounds in P. suffruticosa, paeoniflorin and oxypaeoniflora, on advanced glycation end products-induced mesangial cell damage. In the present study, we investigated the protective activities of paeoniflorin and oxypaeoniflora on advanced glycation end product-induced oxidative stress and inflammation in mesangial cells HBZY-1. The IC50 values of paeoniflorin and oxypaeoniflora for inhibiting 2,2'-azinobis-(3-thylbenzothiazoline-6-sulfonic acid) formation were 4.197 × 10-4 M and 1.002 × 10-4 M, respectively. The pretreatment with paeoniflorin and oxypaeoniflora (10-8-10-4 M) significantly increased advanced glycation end product-induced glutathione peroxidase and catalase activities. In the coculture system of HBZY-1 and macrophages, paeoniflorin and oxypaeoniflora could inhibit remarkably the migration of macrophages. Furthermore, paeniflorin and oxypaeniflora attenuated markedly advanced glycation end products-induced inflammation cytokines interleukin-6 and monocyte chemoattractant protein-1 levels in ELISA and western blot analysis in a dose-dependent manner. Taken together, our data provided the reliable evidence that paeniflorin and oxypaeniflora were able to attenuate advanced glycation end products-induced oxidative damage and inflammation in mesangial cells. Paeniflorin and oxypaeniflora might therefore have a beneficial effect in the treatment of diabetic nephropathy.

A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line.

Experiments were conducted to evaluate the induction of apoptosis and the immunomodulatory activities of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves (ASL). Importantly, their possible synergistic properties were also explored in this study. Human lung adenocarcinoma cell line A549 and Lewis tumor-bearing C57BL/6 mice were used for the evaluation of their activities. A MTT assay was used to determine the proliferation inhibition in A549 cells. Annexin-V/PI double staining as well as flow cytometry was performed to detect apoptosis and cell cycle status. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the levels of inflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum. Furthermore, western blot analysis was applied to evaluate the expressions of proteins associated with cell death. Alkaloids or triterpenes showed a high anti-proliferative activity in A549 cells, with IC50 values of 14.4 µg/mL and 9.3 µg/mL, respectively. The alkaloids and triterpenes combination could significantly inhibit tumor growth in tumor-bearing C57BL/6 mice, compared with alkaloids or triterpenes alone (7.5, 15, 30 g raw material/kg). The immune organs indexes including spleen index and thymus index were increased remarkably by the combination of alkaloids and triterpenes, whereas the levels of IL-6 and TNF-α were up-regulated significantly. Moreover, Annexin-V/PI double staining and flow cytometry showed that the combination of alkaloids and triterpenes (1, 2 and 3 mg raw material/kg) could induce apoptosis and cause S cell cycle arrest in A549 cells. Western blot analysis also showed that their combination (2 mg raw material/kg) significantly down-regulated Bcl-2 expression and pro-casp8 level, whereas it remarkably increased the level of cleaved caspase-8 leading to apoptosis in A549 cells. These observations provide preliminary evidence that both alkaloids and triterpenes possess immune regulation and induction apoptosis activities. Their combination has a stronger activity than that of either class alone. Our findings suggested that these components might be beneficial for the prevention and treatment of NSCLC through a significant synergy effect.

Anti-lung cancer activity through enhancement of immunomodulation and induction of cell apoptosis of total triterpenes extracted from Ganoderma luncidum (Leyss. ex Fr.) Karst.

Ganoderma luncidum (Leyss. ex Fr.) Karst. (GLK) has been used traditionally for the prevention and treatment of cancers or tumors for a long time in Traditional Chinese Medicine. The triterpenes as main effective components of GLK have been found to be beneficial for the efficacy. The purpose of this study was to examine the anti-lung cancer activity of triterpenes of GLK in vitro and in vivo and to explore their anti-lung cancer effects and potential mechanisms. A549 cells and Lewis tumor-bearing mice were used to evaluate the inhibition effects of triterpenes on cell proliferation and tumor growth. The IC50 of triterpenes of GLK on A549 cells was 24.63 µg/mL. Triterpenes of GLK could significantly inhibit tumor growth in mice (30, 60 and 120 mg/kg). The immune organs indexes including spleen and thymus were increased remarkedly by the treatment with triterpenes. Moreover, they were able to stimulate the immune response by increasing the expressions of IL-6 and TNF-α. Flow cytometric analysis revealed that cell arrest caused by triterpenes treatment (7.5, 15 and 30 µg/mL) was in the G2/M phase in A549 cells. Triterpenes induced apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and pro-caspase 9 and increasing the levels of cleaved-caspase 9. Our findings suggested that the triterpenes of GLK have anti-lung cancer activity in vitro and in vivo via enhancement of immunomodulation and induction of cell apoptosis. The study provides insights into the mechanism of GLK in the prevention and treatment of lung cancer.