An overview of the research progress on Aconitum carmichaelii Debx.:active compounds, pharmacology, toxicity, detoxification, and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debx. is the most widely distributed species of Aconitum plants in China and has a long history of medicinal use. Because of its toxicity, A. carmichaelii is classified as lower class in the Shennong Bencao Jing (Shennong's Classic of Materia Medica). According to the theory of Chinese medicine, the roots can be used to revive yang for resuscitation, dispel wind, remove dampness, and relieve pain. AIMS OF THE REVIEW: This review focuses on summarizing the latest reports on the components, pharmacology, toxicity, detoxification mechanism and application of A. carmichaelii. It aims to provide ideas for in-depth research on activity mechanism of A. carmichaelii and expanding the value of exploitation and utilization. MATERIALS AND METHODS: Information was collected from the following online scientific databases: PubMed, Web of Science, Wiley Online Library, SciFinder, Scopus, PubChem, China National Knowledge Internet (CNKI), etc. Additional data were obtained from other Chinese medicine books. RESULTS: In this review, 224 compounds were categorized and new compounds discovered in the last five years were highlighted. The main components of A. carmichaelii are C19-diterpene alkaloids(C19-DAs), among which diester-type aconitine is the most toxic and also the main active ingredient, while monoester diterpene alkaloids (MDAs) and aminol diterpene alkaloids (ADAs) are greatly toxicity reduced due to the loss of ester bond. Heating and compatibility are the means to increase the efficiency and reduce the toxicity of A. carmichaelii. In addition, it also contains abundant C20-diterpene alkaloids (C20-DAs). Like C19-DAs, these compounds also have cardiotonic, anticancer, anti-inflammatory and analgesic pharmacological effects, but their toxicity is weaker. The above-ground part contains not only a variety of MDAs and ADAs, but also contains abundant non-diterpenoid alkaloids and active polysaccharides. In addition to pharmacological effects, we further summarized the mechanisms of cardiotoxicity, neurotoxicity and other toxicity of A. carmichaelii. What's more, the application prospects are also discussed. Polysaccharides and diterpenoid alkaloids in A. carmichaelii and related traditional prescriptions have great promising prospects for the development of new drugs. CONCLUSION: A. carmichaelii has rich alkaloids and polysaccharides, but the new compounds discovered in recent years are only in the activity screening stage. The toxic differences between C19- and C20- DAs and the dose that affect toxicity of A. carmichaelii are still not clear. The non-traditional medicinal parts, such as stems and leaves, show great potential for development and utilization. More extensive and in-depth exploration of low-toxic active compounds, as well as the mechanism of efficacy-enhancement and toxicity-attenuation, will help A. carmichaelii to be better and safer used for clinical.

Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adipose-liver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and FMT. Understanding the immunological mechanisms underlying in SLD is crucial for advancing clinical therapeutic strategies.

Formosanin C inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1.

BACKGROUND: Cisplatin (DDP) as the first-line drug has been used in cancer therapy. However, side effects and drug resistance are the challenges of DDP. Disordered lipid metabolism is related to DDP resistance. STUDY DESIGN: In this study, formosanin C (FC) as the main compound of Rhizoma Paridis saponins (RPS) inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1. METHODS AND RESULTS: RPS prolonged the survival period of mice, reduced pulmonary metastases and alleviated colon toxicity caused by DDP. FC as the main compound of RPS enhanced the anti-tumor and anti-metastatic effects of DDP. FC decreased the mRNA level of SCD1 and the content of lipid droplets (LDs) in lung cancer cells. Molecular dynamics and isothermal titration calorimetry verified the binding stability and spontaneously between FC and SCD1. SiSCD1 reduced the content of LDs in cell lines and increased mitochondria (mtROS), which was consistent with the results of FC treatment. The combination group decreased DNA repair associated protein as well as DDP resistance markers such as ERCC1 and 53bp1, and increased DNA damage marker like γH2AX, which indirectly confirmed the occurrence of mtROS. In addition, FC combination with DDP also affected epithelial-mesenchymal transition-related protein like VIM and CDH1 in vivo experiments, and thereby inhibited pulmonary metastasis. CONCLUSION: Our research indicated that the FC as the main compound of RPS targeted the CY2 domain of SCD1, inhibited lipid metabolism in mice, and thereby suppressed cancer metastases. This provided support for use of FC to treat cancer based on lipid metabolism pathway.

Pectin: Health-promoting properties as a natural galectin-3 inhibitor.

Galectin-3 has a variety of important pathophysiological significance in the human body. Much evidence shows that the abnormal expression of galectin-3 is related to the formation and development of many diseases. Pectin is mostly obtained from processed citrus fruits and apples and is a known natural inhibitor of galactin-3. A large number of peels produced each year are discarded, and it is necessary to recycle some of the economically valuable active compounds in these by-products to reduce resource waste and environmental pollution. By binding with galectin-3, pectin can directly reduce the expression level of galectin-3 on the one hand, and regulate the expression level of cytokines by regulating certain signaling pathways on the other hand, to achieve the effect of treating diseases. This paper begins by presenting an overview of the basic structure of pectin, subsequently followed by a description of the structure of galectin-3 and its detrimental impact on human health when expressed abnormally. The health effects of pectin as a galectin-3 inhibitor were then summarized from the perspectives of anticancer, anti-inflammatory, ameliorating fibrotic diseases, and anti-diabetes. Finally, the challenges and prospects of future research on pectin are presented, which provide important references for expanding the application of pectin in the pharmaceutical industry or developing functional dietary supplements.

Evaluation of citrus pectin extraction methods: Synergistic enhancement of pectin's antioxidant capacity and gel properties through combined use of organic acids, ultrasonication, and microwaves.

The biological potency of pectin is intricately intertwined with its intricate molecular architecture. The fine structure of pectin is influenced by the extraction method, while the specific impact of these methods on the fine structure and the affected attributes thereof remains enigmatic. This study delves into the profound analysis of eight distinct extraction methods influence on the structure and biological activity of citrus peel pectin. The findings demonstrate that citric acid ultrasound-assisted microwave extraction yields pectin (PectinCA-US/MV) with higher viscosity and a dense, rigid chain. Pectin extracted with acetic acid ultrasound (PectinAA-US) and citric acid ultrasound (PectinCA-US) exhibits elevated galacturonic acid (GalA) levels and reduced D-galactose (Gal) content, enhancing antioxidant activity. Eight pectin-chitosan (CS) hydrogels, especially PectinCA-US/MV-CS, demonstrate commendable thermal stability, rheological properties, self-healing capability, and swelling behavior. This study characterizes citrus peel pectin properties from different extraction methods, laying a foundation for its application in food, pharmaceuticals, and industry.

The lipid droplet in cancer: From being a tumor-supporting hallmark to clinical therapy.

INTRODUCTION: Abnormal lipid metabolism, one of the hallmarks in cancer, has gradually emerged as a novel target for cancer treatment. As organelles that store and release excess lipids, lipid droplets (LDs) resemble "gears" and facilitate cancer development in the body. AIM: This review discusses the life cycle of LDs, the relationship between abnormal LDs and cancer hallmarks, and the application of LDs in theragnostic and clinical contexts to provide a contemporary understanding of the role of LDs in cancer. METHODS: A systematic literature search was conducted in PubMed and SPORTDiscus. Retrieve and summarize clinical trials of drugs that target proteins associated with LD formation using the Clinical Trials website. Create a schematic diagram of lipid droplets in the tumor microenvironment using Adobe Illustrator. CONCLUSION: As one of the top ten hallmarks of cancer, abnormal lipid metabolism caused by excessive generation of LDs interrelates with other hallmarks. The crosstalk between excessive LDs and intracellular free fatty acids (FFAs) promotes an inflammatory environment that supports tumor growth. Moreover, LDs contribute to cancer metastasis and cell death resistance in vivo. Statins, as HMGCR inhibitors, are promising to be the pioneering commercially available anti-cancer drugs that target LD formation.

Recent Advances in Reprogramming Strategy of Tumor Microenvironment for Rejuvenating Photosensitizers-Mediated Photodynamic Therapy.

Photodynamic therapy (PDT) has recently been considered a potential tumor therapy due to its time-space specificity and non-invasive advantages. PDT can not only directly kill tumor cells by using cytotoxic reactive oxygen species but also induce an anti-tumor immune response by causing immunogenic cell death of tumor cells. Although it exhibits a promising prospect in treating tumors, there are still many problems to be solved in its practical application. Tumor hypoxia and immunosuppressive microenvironment seriously affect the efficacy of PDT. The hypoxic and immunosuppressive microenvironment is mainly due to the abnormal vascular matrix around the tumor, its abnormal metabolism, and the influence of various immunosuppressive-related cells and their expressed molecules. Thus, reprogramming the tumor microenvironment (TME) is of great significance for rejuvenating PDT. This article reviews the latest strategies for rejuvenating PDT, from regulating tumor vascular matrix, interfering with tumor cell metabolism, and reprogramming immunosuppressive related cells and factors to reverse tumor hypoxia and immunosuppressive microenvironment. These strategies provide valuable information for a better understanding of the significance of TME in PDT and also guide the development of the next-generation multifunctional nanoplatforms for PDT.

Effect of Cerebralcare Granule® combined with memantine on Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: In elderly people, Alzheimer's disease (AD) is the most common form of dementia. It has been shown that traditional Chinese medicine (TCM) based on phytomedicines enhances the therapeutic effects of modern medicine when taken in conjunction with them. Modern medicine N-methyl-D-aspartate receptor (NMDA) antagonist memantine (Mm) are mainly used in the clinical treatment of AD. TCM Cerebralcare Granule® (CG) has long been an effective treatment for headaches, dizziness, and other symptoms. In this study, we employ a blend of CG and Mm to address Alzheimer's disease-like symptoms and explore their impacts and underlying mechanisms. AIM OF THE STUDY: The objective of our study was to observe the effects of CG combined with Memantine (Mm) on learning and memory impairment of AD mice induced by D-galactose and to explore the mechanism at work. MATERIALS AND METHODS: CG and Mm were combined to target multiple pathological processes involved in AD. For a thorough analysis, we performed various experiments such as behavioral detection, pathological detection, proteomic detection, and other experimental methods of detection. RESULTS: It was found that the combination of CG and Mm was significantly effective for improving learning and memory in AD mice as well as brain pathology. The serum and hippocampal tissue of AD mice were significantly enhanced with catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels were decreased with this treatment. In AD mice, a combination of Mm and CG (CG + Mm) significantly increased the levels of the anti-inflammatory factors IL-4 and IL-10, decreased the levels of pro-inflammatory factors (IL-6, IL-1ß) and tumor necrosis factor-alpha (TNF-α), improved synaptic plasticity by restoring synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) expression in the hippocampus, enhanced Aß phagocytosis of microglia in AD mice, and increased mitochondrial respiratory chain enzyme complexes I, II, III, and IV, lead to an increase in the number of functionally active NMDA receptors in the hippocampus. Proteomic analysis GO analysis showed that the positive regulation gene H3BIV5 of G protein coupled receptor signal pathway and synaptic transmission was up-regulated, while the transsynaptic signal of postsynaptic membrane potential and regulation-related gene Q5NCT9 were down-regulated. Most proteins showed significant enriched signal transduction pathway profiles after CG + Mm treatment, based on the KEGG pathway database. CONCLUSION: The data supported the idea that CG and Mm could be more effective in treating AD mice induced by D-galactose than Mm alone. We provided a basis for the clinical use of CG with Mm.

A new insight into material basis of rhizoma Paridis saponins in alleviating pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla, as a traditional Chinese herbal medicine, was often used to relieve inflammation and pain. Rhizoma Paridis saponins (RPS) as the main active components of Paris polyphylla have excellent analgesic effects. AIM OF THE STUDY: Determine the analgesic material basis of RPS. MATERIALS AND METHODS: LC-MS/MS was used to analyze RPS, plasma after intravenous injection of RPS, and oral administration of RPS. H22 plantar pain model was established to explore the analgesic material basis of RPS. Moreover, correlation analysis, network pharmacology, RT-PCR and molecular docking were applied in this research. RESULTS: RPS had dose-dependently analgesic effects in acetic acid- and formalin-induced pain models. LC-MS/MS detection indicated that diosgenin as the metabolite of RPS mainly distributed in brain tissues. The addition of antibiotics increased the anti-tumor effect of RPS, but reduced its analgesic effect. Network pharmacology, RT-PCR and molecular docking showed that diosgenin exerted its analgesic effect through SRC and Rap1 signaling pathway. CONCLUSION: Diosgenin exhibited analgesic effects, while saponins had good anti-tumor effects in RPS. This discovery provided a better indication for the later application of RPS in anti-tumor and analgesic settings.

Gut liver brain axis in diseases: the implications for therapeutic interventions.

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, ß-amyloid (Aß) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aß metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

Dual targeting of wild-type p53 and gut microbiota by Magnolol represses key metabolic process and kills CRC cells.

Cancer cells consume considerable glucose quantities and majorly employ glycolysis for ATP generation. This metabolic signature (the Warburg effect) allows cancer cells to channel glucose to biosynthesis to support and maintain their dramatic growth along with proliferation. Currently, our understanding of the metabolic and mechanistic implications of the Warburg effect along with its relationship with biosynthesis remains unclear. Herein, we illustrate that the tumor repressor p53 mediate Magnolol (MAG) triggers colon cancer cell apoptosis. And MAG regulates the glycolytic and oxidative phosphorylation steps through transcriptional modulation of its downstream genes TP53-induced glycolysis modulator and biosynthesis of cytochrome c oxidase, attenuating cell proliferation and tumor growth in vivo and in vitro. Meanwhile, we show that MAG cooperates with its own intestinal microflora characteristic metabolites to repress tumors, especially remarkably declined kynurenine (Kyn)/tryptophan (Trp) ratio. Besides, strong relationships of MAG influenced genes, microbiota, as well as metabolites, were explored. Therefore, we established that p53-microbiota-metabolites function as a mechanism, which enable therapy approaches against metabolism-implicated colorectal cancer, in particular MAG as a prospective candidate for treating colorectal cancer.

Naturally and chemically acetylated polysaccharides: Structural characteristics, synthesis, activities, and applications in the delivery system: A review.

Acetylated polysaccharides refer to polysaccharides containing acetyl groups on sugar units. In the past, the acetylation modification of wall polysaccharides has been a hot research topic for scientists. However, in recent years, many studies have reported that acetylation-modified plant, animal, and microbial polysaccharide show great potential in delivery systems. From the latest perspective, this review systematically presents the different sources of naturally acetylated polysaccharides, the regularity of their modification, the chemical preparation of acetylation modifications, the biological activities and functions of acetylated polysaccharides, and the application in the delivery system. In nature, acetylated polysaccharides are extensively distributed in plants, microorganism, and animals. The level of acetylation modification, the distribution of chains, and the locations of acetylation modification sites differ between species. An increasing number of acetylated polysaccharides were prepared in the aqueous medium, which is safe, environment friendly, and low-cost. In addition to being necessary for plant growth and development, acetylated polysaccharides have immunomodulatory, antioxidant, and anticancer properties. The above-mentioned multiple sources, multifunctional and multi-active acetylated polysaccharides, make them an increasingly important part of delivery systems. We conclude by discussing the future directions for research and development and the potential uses for acetylated polysaccharides.

Diosgenin relieves oxaliplatin-induced pain by affecting TLR4/NF-κB inflammatory signaling and the gut microbiota.

Diosgenin extracted from fenugreek, yam and other foods exhibits a wide range of pharmacological activities, especially for the treatment of pain and other nervous system diseases. However, its role in oxaliplatin-induced peripheral neuropathy (OIPN) is unclear. To explore its detailed mechanism on the pain caused by chemotherapy, we carried out this experiment. In this study, the effects of diosgenin on injured PC12 cells and OIPN mice were examined. The results showed that diosgenin not only protected PC12 from injury, but also reduced the mechanical withdrawal threshold and cold hyperalgesia in OIPN mice. Diosgenin inhibited oxidative stress, the cell glial fibrillary acidic protein, and the pro-inflammatory cytokines such as tumor necrosis factor-α, toll-like receptor 4 and nuclear factor-κB in the brain. Furthermore, the fecal microbiota transplantation experiment indicated that diosgenin improved OIPN through regulation of the gut microbiota. All in all, diosgenin ameliorates peripheral neuropathy and is worthy of further study in the treatment of neuropathic pain.

Mitochondria-targeted pentacyclic triterpenoid carbon dots for selective cancer cell destruction via inducing autophagy, apoptosis, as well as ferroptosis.

Natural products have been an important database for anti-cancer drug development. However, low water solubility and poor biocompatibility limit the efficacy of natural products. Carbon dots (CDs), as an emerging 0D material, have unique properties in bioimaging, water solubility and biocompatibility. Here, we prepared three pentacyclic triterpenoids (PTs) included glycyrrhetinic acid (GA), ursolic acid (UA) and oleanolic acid (OA), which have anticancer activity but poor water solubility, as raw materials into CDs to improve disadvantages. Our data indicated that the active surface groups of all three CDs were largely preserved and were able to excite green fluorescence. Their carboxyl edges not only exhibited excellent water solubility, but also specifically targeted tumor cell mitochondria due to high sensitivity to ROS-induced damage and high internal oxidative stress. In cancer cells, the PT-CDs induced cell death through three pathways (apoptosis, ferroptosis, and autophagy), which is essentially the same way their raw materials induce death, but the effect was much stronger than raw materials. Notably, functionalized PT-CDs also exhibited extremely low toxicity. In summary, PT-CDs not only have improved water solubility and biocompatibility, but also retain the structure of their raw materials well and exert better efficacy, which provides new ideas for the development of anti-cancer natural product drugs.

Melanin-like nanoparticles: advances in surface modification and tumour photothermal therapy.

Currently, tumor treatments are characterized by intelligence, diversity and personalization, but the therapeutic reagents used are often limited in clinical efficacy due to problems with water solubility, targeting, stability and multidrug resistance. To remedy these shortcomings, the application of multifunctional nanotechnology in the biomedical field has been widely studied. Synthetic melanin nanoparticles (MNPs) surfaces which contain highly reactive chemical groups such as carboxyl, hydroxyl and amine groups, can be used as a reaction platform on which to graft different functional components. In addition, MNPs easily adhere to substrate surface, and serve as a secondary reaction platform to modify it. The multifunctionality and intrinsic biocompatibility make melanin-like nanoparticles promising as a multifunctional and powerful nanoplatform for oncological applications. This paper first reviews the preparation methods, polymerization mechanisms and physicochemical properties of melanin including natural melanin and chemically synthesized melanin to guide scholars in MNP-based design. Then, recent advances in MNPs especially synthetic polydopamine (PDA) melanin for various medical oncological applications are systematically and thoroughly described, mainly focusing on bioimaging, photothermal therapy (PTT), and drug delivery for tumor therapy. Finally, based on the investigated literature, the current challenges and future directions for clinical translation are reasonably discussed, focusing on the innovative design of MNPs and further elucidation of pharmacokinetics. This paper is a timely and comprehensive and detailed study of the progress of MNPs in tumor therapy, especially PTT, and provides ideas for the design of personalized and customizable oncology nanomedicines to address the heterogeneity of the tumor microenvironment.

Engineering of triterpene metabolism and overexpression of the lignin biosynthesis gene PAL promotes ginsenoside Rg3 accumulation in ginseng plant chassis.

The ginsenoside Rg3 found in Panax species has extensive pharmacological properties, in particular anti-cancer effects. However, its natural yield in Panax plants is limited. Here, we report a multi-modular strategy to improve yields of Rg3 in a Panax ginseng chassis, combining engineering of triterpene metabolism and overexpression of a lignin biosynthesis gene, phenylalanine ammonia lyase (PAL). We first performed semi-rational design and site mutagenesis to improve the enzymatic efficiency of Pq3-O-UGT2, a glycosyltransferase that directly catalyzes the biosynthesis of Rg3 from Rh2 . Next, we used clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing to knock down the branch pathway of protopanaxatriol-type ginsenoside biosynthesis to enhance the metabolic flux of the protopanaxadiol-type ginsenoside Rg3 . Overexpression of PAL accelerated the formation of the xylem structure, significantly improving ginsenoside Rg3 accumulation (to 6.19-fold higher than in the control). We combined overexpression of the ginsenoside aglycon synthetic genes squalene epoxidase, Pq3-O-UGT2, and PAL with CRISPR/Cas9-based knockdown of CYP716A53v2 to improve ginsenoside Rg3 accumulation. Finally, we produced ginsenoside Rg3 at a yield of 83.6 mg/L in a shake flask (7.0 mg/g dry weight, 21.12-fold higher than with wild-type cultures). The high-production system established in this study could be a potential platform to produce the ginsenoside Rg3 commercially for pharmaceutical use.

Comparison of characterization and antioxidant activity of different citrus peel pectins.

Pectins obtained from citrus peel of different cultivars and growth regions were compared based on physicochemical properties and antioxidant activity in vitro. The physicochemical features were elucidated using Fourier transform infrared (FT-IR), molecular weight distribution, monosaccharide composition, thermal behaviors and flow behaviors. Results showed that the different cultivars and growing areas have significant effects on the properties of citrus peel pectins (CPPs). Citrus peel pectins extracted by acetic acid were highly heterogeneous polysaccharides with broad molecular weight distributions and had high proportions of the RG-I domain. Among the 10 kinds of citrus peel pectins, Shatangju (CPP-6) and Xuecheng (CPP-7) own superior antioxidant biological activity and Dahongpao (CPP-3) and Buzhihuo (CPP-9) had excellent functional properties (thermal stability and viscosity). According to the correlation analysis, molecular weight, galacturonic acid content and degree of methyl-esterification were beneficial to increase the thermal stability and viscosity of citrus peel pectins, while the rhamnose content, rhamnogalacturonan I region and lower molecular weight can improve citrus peel pectins antioxidant activity. Our findings suggest that CPP-6 and CPP-7 may be useful as a potential natural antioxidant in pharmaceutical and cosmetic industries. Meanwhile, CPP-3 has great application potential in high temperature food and CPP-9 can be used as a thickener or stabilizer in the food industry.

Q-marker identification of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. in pulmonary metastasis of liver cancer mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Paridis saponins (RPS) as the mainly active components of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz., possess tumor therapeutic potential. However, the anti-tumor material basis of RPS in liver cancer pulmonary metastasis remains poorly understood. The objective of this study was to identify the distribution and anti-cancer effects of RPS in liver cancer pulmonary metastatic model. MATERIALS AND METHODS: In this study, a mouse liver cancer pulmonary metastasis model was established to determine the distribution of different saponins in the tissues by UPLC-MS and plasma protein binding rate. RESULTS: As a result, RPS prolonged the survival time and inhibited the pulmonary metastasis in H22 injected mice through its underlying mechanism. UPLC-MS identified saponins from RPS such as PVII, PH, PVI, PII, gracillin and PI in tissues, which may be regarded as the Q-markers in RPS. Surprisingly, the concentration of PI, PII and gracillin as diosgenyl saponins was higher than that of pennogenyl saponins in the liver and lung. Besides, plasma protein binding rate of PII was higher than that of PVII. CONCLUSION: These findings suggested that PVII, PH, PVI, PI, PII and gracillin are regarded as the Q-markers of RPS in liver cancer pulmonary metastasis. The concentration of PI, PII and gracillin as diosgenyl saponins was higher than that of pennogenyl saponins in the liver and lung. It would be helpful for understanding the importance of RPS with anticancer activities in the future.

Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer.

Nanomedicine, constructed from therapeutics, presents an advantage in drug delivery for cancer therapies. However, nanocarrier-based treatment systems have problems such as interbatch variability, multicomponent complexity, poor drug delivery, and carrier-related toxicity. To solve these issues, the natural molecule honokiol (HK), an anticancer agent in a phase I clinical trial (CTR20170822), was used to form a self-assembly nanoparticle (SA) through hydrogen bonding and hydrophobicity. The preparation of SA needs no molecular precursors or excipients in aqueous solution, and 100% drug-loaded SA exhibited superior tumor-targeting ability due to the enhanced permeability and retention (EPR) effect. Moreover, SA significantly enhanced the antitumor immunity relative to free HK, and the mechanism has notable selectivity to the p53 pathway. Furthermore, SA exhibited excellent physiological stability and inappreciable toxicity. Taken together, this supramolecular self-assembly strategy provides a safe and "molecular economy" model for rational design of clinical therapies and is expected to promote targeted therapy of HK, especially in colorectal cancer patients with obvious p53 status.

Effects of Metal Nanoparticles and Other Preparative Materials in the Environment on Plants: From the Perspective of Improving Secondary Metabolites.

The influence of preparation material residues in wastewater and soil on plants has been paid more and more attention by researchers. Secondary metabolites play an important role in the application of plants. It was found that nanomaterials can increase the content of plant secondary metabolites in addition to their role in pharmaceutical preparations. For example, 800 mg/kg copper oxide nanoparticles (NPs) increased the content of p-coumaric acid in cucumber by 225 times. Nanoparticles can cause oxidative stress in plants, increase signal molecule, and upregulate the synthase gene expression, increasing the content of secondary metabolites. The increase of components such as polyphenols and total flavonoids may be related to oxidative stress. This paper reviews the application and mechanism of metal nanomaterials (Ag-NP, ZnO-NP, CeO2-NP, Cds-NP, Mn-NP, CuO-NP) in promoting the synthesis of secondary metabolites from plants. In addition, the effects of some other preparative materials (cyclodextrins and immobilized molds) on plant secondary metabolites are also involved. Finally, possible future research is discussed.