Ginkgetin effectively mitigates collagen and AA-induced platelet activation via PLCγ2 but not cyclic nucleotide-dependent pathway in human.

Platelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5-1 µM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK's influence. GK's modulatory effect extended to ATP release, P-selectin expression, intracellular calcium ([Ca2+ ]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß and mitogen-activated protein kinases. GK's antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator-stimulated phosphoproteinSer157 or Ser239 . Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK's profound impact on platelet activation, achieved through inhibiting PLCγ2-PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs.

"Multi-in-One" Yolk-Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade Reactions.

Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2 O2 ) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.

Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.

BACKGROUND: In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism. METHODS: We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1. RESULTS: HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.

Oridonin ameliorates renal fibrosis in diabetic nephropathy by inhibiting the Wnt/ß-catenin signaling pathway.

Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/ß-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro, HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of ß-catenin arrested cell migration and reduced the expression levels of Wnt/ß-catenin signaling-related molecules (Wnt4, p-GSK3ß and ß-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of ß-catenin. Furthermore, the combination of Ori treatment and ß-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/ß-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.

A new coumarin and a new flavonoid from Ochrocarpus longifolius.

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models.

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 µM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

[Development of green pesticides from traditional Chinese medicines based on artificial intelligence and compatibility of traditional Chinese medicines].

The food security of China as a big agricultural country is attracting increasing attention. With the progress in the traditional Chinese medicine industry, Chinese medicinal materials and their preparations have been gradually developed as agents for disease prevention and with antimicrobial and insecticidal functions in agriculture. Promoting pesticide innovation by interdisciplinary integration has become the trend in pesticide research globally. Considering the increasingly important roles of green pesticides from traditional Chinese medicines and artificial intelligence in pest target prediction, this paper proposed an innovative green control strategy in line with the concepts of ecological sustainable development and food security protection. CiteSpace was used for visual analysis of the publications. The results showed that artificial intelligence had been extensively applied in the pesticide field in recent years. This paper explores the application and development of biopesticides for the first time, with focus on the plant-derived pesticides. The thought of traditional Chinese medicine compatibility can be employed to creat a new promosing field: pesticides from traditional Chinese medicine. Moreover, artificial intelligence can be employed to build the formulation system of pesticides from traditional Chinese medicines and the target prediction system of diseases and pests. This study provides new ideas for the future development and market application of biopesticides, aiming to provide more healthy and safe agricultural products for human beings, promote the innovation and development of green pesticides in China, and protect the sustainable development of the environment and ecosystem. This may be the research hotspot and competition point for the green development of the pesticide industry chain in the future.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

AuPt-Loaded Cu-Doped Polydopamine Nanocomposites with Multienzyme-Mimic Activities for Dual-Modal Imaging-Guided and Cuproptosis-Enhanced Photothermal/Nanocatalytic Therapy.

Nanocatalytic therapy (NCT) has made great achievements in tumor treatments due to its remarkable enzyme-like activities and high specificity. Nevertheless, the limited types of nanozymes and undesirable tumor microenvironments (TME) greatly weaken the therapeutic efficiency. Developing a combination therapy integrating NCT and other strategies is of great significance for optimal treatment outcomes. Herein, a AuPt-loaded Cu-doped polydopamine nanocomposite (AuPt@Cu-PDA) with multiple enzyme-like activities was rationally designed, which integrated photothermal therapy (PTT) and NCT. The peroxidase (POD)-like activity of AuPt@Cu-PDA can catalyze hydrogen peroxide (H2O2) into ·OH, and the catalase (CAT)-mimic activity can decompose H2O2 into O2 to alleviate hypoxia of TME, and O2 can be further converted into toxic ·O2- by its oxidase (OXD)-mimic activity. In addition, Cu2+ in AuPt@Cu-PDA can effectively consume GSH overexpressed in tumor cells. The boosting of reactive oxygen species (ROS) and glutathione (GSH) depletion can lead to severe oxidative stress, which can be enhanced by its excellent photothermal performance. Most importantly, the accumulation of Cu2+ can disrupt copper homeostasis, promote the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), disrupt the mitochondrial tricarboxylic acid (TCA) cycle, and finally result in cuproptosis. Collectively, photothermal and photoacoustic imaging (PTI/PAI)-guided cuproptosis-enhanced NCT/PTT can be achieved. This work may expand the application of nanozymes in synergistic therapy and provide new insights into cuproptosis-related therapeutic strategies.

[Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro].

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-ß-boswellic(KBA), and 3-acetyl-11-keto-ß-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

[High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon"].

In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.

[Measures for waste and by-product recycling and circular economy of whole industry chain of traditional Chinese medicine resources facing carbon peak and carbon neutrality (dual carbon) goals].

It has become a common consensus that resource conservation and intensive recycling for improving resource utilization efficiency is an important way to achieve carbon peak and carbon neutrality(dual carbon). Traditonal Chinese medicine(TCM)resources as national strategic resources are the material basis and fundamental guarantee for the development of TCM industry and health services. However, the rapid growth of China's TCM industry and the continuous expansion and extension of the industrial chain have exposed the low efficiency of TCM resources. Resource waste and environmental pollution caused by the treatment and discharge of TCM waste have emerged as major problems faced by the development of the industry, which has aroused wide concern. Considering the dual carbon goals, this paper expounds the role and potential of TCM resource recycling and circular economy industry development. Taking the typical model of TCM resource recycling as the case of circular economy industry in reducing carbon source and increasing carbon sink, this paper puts forward the suggestions for the TCM circular economy industry serving the double carbon goals. The suggestions mainly include strengthening the policy and strategic leading role of the double carbon goals, building an objective evaluation system of low-carbon emission reduction in the whole industrial chain of TCM resources, building an industrial demonstration park for the recycling of TCM resources, and promoting the establishment of a circular economy system of the whole industrial chain of TCM resources. These measures are expected to guide the green transformation of TCM resource industry from linear economic model to circular economy model, provide support for improving the utilization efficiency and sustainable development of TCM resources, and facilitate the low-carbon and efficient development of TCM resource industry and the achievement of the double carbon goals.

circ_0089153 exacerbates breast cancer cells proliferation and metastasis via sponging miR-2467-3p/E2F6.

The role of circ_0089153 in breast cancer (BCa) malignancy development was explored. circ_0089153 expression in BCa was analyzed by Gene Expression Omnibus database. Clinical tissues were obtained from 90 BCa patients. Cell counting kit-8 assay, 5-ethnyl-2 deoxyuridine assay and colony formation experiment were applied for proliferation detection. Wound healing assay and Transwell experiment were used for migration and invasion detection. Dual luciferase reporter gene assay, RNA immunoprecipitation assay and RNA pull-down assay were conducted. In vivo growth and metastasis of BCa cells were performed. Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were applied for RNAs and proteins expression. The up-modulated circ_0089153 indicated an unfavorable survival of BCa patients. circ_0089153 knockdown attenuated BCa cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < .01). circ_0089153 was miR-2467-3p sponge. Low miR-2467-3p expression indicated a worse survival of BCa patients. miR-2467-3p overexpression reduced BCa cells proliferation, migration, invasion and EMT (P < .05). circ_0089153 enhanced BCa cells proliferation, migration, invasion and EMT by sponging miR-2467-3p (P < .05). E2F6 was directly suppressed by miR-2467-3p. E2F6 high expression in BCa patients associated with worse survival. circ_0089153 knockdown suppressed in vivo BCa cells growth and lung metastasis (P < .01). circ_0089153 was an oncogene in breast cancer, which enhanced proliferation and metastasis through sponging miR-2467-3p/E2F6. circ_0089153 was suggested to be a potential target for BCa target treatment.

Effects of Dried Onion Powder and Quercetin on Obesity-Associated Hepatic Menifestation and Retinopathy.

Onion (Allium cepa L.), rich in flavonoids (particularly quercetin), reportedly has anti-obesity properties, but the underlying mechanisms and associated health issues remain unclear. In this study, we compared the effects of dried onion powder (DO) with that of quercetin on high-fat diet (HFD)-induced obesity, nonalcoholic fatty liver disease, and retinal neovascularization. Briefly, rats (n = 9-10 per group) were divided into control, HFD alone (43% fat), HFD + DO (1% DO), HFD + 5DO (5% DO, w/w), and HFD + quercetin (180 mg/kg). After 12 weeks, body fat, markers of metabolism, fatty liver, steatohepatitis, and retinopathy were analyzed. The results revealed that DO and 5DO dose-dependently suppressed body weight, visceral and subcutaneous fat accumulation, and epididymal adipocyte in HFD-fed rats. DO also decreased HFD-induced ALT, AST, free fatty acid, glucose, proinflammatory cytokines, and oxidative stress. DO and 5DO groups had lower triglycerides, total cholesterol, proinflammatory cytokine levels, and ACC-α (a fatty acid synthesis-associated enzyme) expression but higher hepatic antioxidant enzyme activities and fecal lipids. 5DO exhibited better or similar efficacy to quercetin. Both 5DO and quercetin increased fecal levels of acetic acid and butyric acid similarly. They also reduced lipid peroxidation of the eye, retinal adiposity, and neovascularization. However, quercetin resulted in a more apparent decrease in regulation of the Raf/MAPK pathway than DO in eye specimens. Conclusively, DO suppresses visceral, subcutaneous, and liver fat accumulation better than quercetin likely due to higher fecal fat excretion and lower oxidative stress, proinflammatory cytokine levels, and ACC-α expression. Quercetin regulating signal pathways is better than DO at reducing retinal adiposity and neovascularization.

The Anti-Proliferative and Apoptotic Effects of Rutaecarpine on Human Esophageal Squamous Cell Carcinoma Cell Line CE81T/VGH In Vitro and In Vivo.

The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP's effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.

Evaluation of Anti-Inflammatory and Antioxidant Effectsof Chrysanthemum Stem and Leaf Extract on Zebrafish Inflammatory Bowel Disease Model.

Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1ß, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1ß, IL-8 and MMP9.

[Combination characteristics of frankincense and myrrh and progress and prospect of their combination efficacy and mechanism].

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.

[Identification of metabolites of Yiqi Baoyuan Prescription in rat plasma, bile, urine and feces after oral administration].

This study was designed to determine the metabolites of Yiqi Baoyuan Prescription(YQBYP) in rats. The ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry(UPLC-TOF-MS) and mass defect filter(MDF) were employed to analyze the metabolites of YQBYP in rat plasma, bile, urine and feces. Chromatographic separation was conducted on Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) under gradient elution with 0.1% formic acid aqueous solution(A)-acetonitrile(B), and the column temperature was 30 ℃. Electrospray ion(ESI) source was used under positive and negative ion modes, with capillary voltage of 3.0 kV and mass scanning range of m/z 100-1 000. In this experiment, 9 prototype components and 36 metabolites were identified in rat plasma, bile, urine and feces samples. The results showed that the main metabolic pathways of YQBYP in rats involved methylation, demethylation, oxidation, and other phase Ⅰ reactions as well as glucuronidation, sulfation, and other phase Ⅱ reactions. This study provided scientific basis for clarifying the therapeutic material basis of YQBYP and product development.

Quercetin attenuates cisplatin-induced fat loss.

PURPOSE: The major aim of the present study was to determine the effects of quercetin, a well-known flavonoid, on attenuating cisplatin (CDDP)-induced fat loss and the possible mechanisms. METHODS: Tumor-bearing nude mice and tumor-free BALB/c mice were administrated with CDDP alone or in combination with quercetin by a diet containing 0.1% or 1% quercetin (LQ or HQ) or by intraperitoneal injection (IQ) to determine the effects of quercetin on the anticancer effect of CDDP or CDDP-induced fat loss. The effects of quercetin on fat accumulation in CDDP-exposed 3T3-L1 cells were also determined. RESULTS: We first showed that HQ and IQ significantly enhanced the anticancer effect of CDDP by upregulating p53- and p21-associated pathways, while tended to attenuate CDDP-induced fat loss in tumor-bearing nude mice. The study in 3T3-L1 cells showed that CDDP decreased the fat accumulation accompanied by strong upregulation of the expression of six genes which are associated with fat metabolism, while quercetin completely suppressed such an effect. The tumor-free BALB/c mice study consistently showed a protective effect of HQ on CDDP-induced body weight and epididymal fat loss. HQ also increased the fat levels in liver and muscle tissues. In epididymal fat tissues, HQ consistently attenuated CDDP-induced changes in fat metabolism-associated gene expression. However, CDDP alone or in combination with HQ did not affect the food intake. CONCLUSIONS: This study demonstrates that quercetin possesses the potential to suppress CDDP-induced fat loss may partly through the regulation of the fat metabolism-associated gene expression.