Green Synthesis of Blumea balsamifera Oil Nanoemulsions Stabilized by Natural Emulsifiers and Its Effect on Wound Healing.

In this study, we developed a green and multifunctional bioactive nanoemulsion (BBG-NEs) of Blumea balsamifera oil using Bletilla striata polysaccharide (BSP) and glycyrrhizic acid (GA) as natural emulsifiers. The process parameters were optimized using particle size, PDI, and zeta potential as evaluation parameters. The physicochemical properties, stability, transdermal properties, and bioactivities of the BBG-NEs under optimal operating conditions were investigated. Finally, network pharmacology and molecular docking were used to elucidate the potential molecular mechanism underlying its wound-healing properties. After parameter optimization, BBG-NEs exhibited excellent stability and demonstrated favorable in vitro transdermal properties. Furthermore, it displayed enhanced antioxidant and wound-healing effects. SD rats wound-healing experiments demonstrated improved scab formation and accelerated healing in the BBG-NE treatment relative to BBO and emulsifier groups. Pharmacological network analyses showed that AKT1, CXCL8, and EGFR may be key targets of BBG-NEs in wound repair. The results of a scratch assay and Western blotting assay also demonstrated that BBG-NEs could effectively promote cell migration and inhibit inflammatory responses. These results indicate the potential of the developed BBG-NEs for antioxidant and skin wound applications, expanding the utility of natural emulsifiers. Meanwhile, this study provided a preliminary explanation of the potential mechanism of BBG-NEs to promote wound healing through network pharmacology and molecular docking, which provided a basis for the mechanistic study of green multifunctional nanoemulsions.

Contribution of phenolamides to the quality evaluation in Lycium spp.

ETHNOPHARMACOLOGICAL RELEVANCE: Goji berry is a general term for various plant species in the genus Lycium. Goji has long been historically used in traditional Chinese medicines. Goji is a representative tonic medicine that has the effects of nourishing the liver and kidney and benefiting the essence and eyesight. It has been widely used in the treatment of various diseases, including tinnitus, impotence, spermatorrhea and blood deficiency, since ancient times. AIM OF THE REVIEW: This study aims to comprehensively summarize the quality evaluation methods of the main compounds in goji, as well as the current research status of the phenolamides in goji and their pharmacological effects, to explore the feasibility of using phenolamides as quality control markers and thus improve the quality and efficacy in goji. MATERIALS AND METHODS: Relevant literature from PubMed, Web of Science, Science Direct, CNKI and other databases was comprehensively collected, screened and summarized. RESULTS: According to the collected literature, the quality evaluation markers of goji in the Pharmacopoeia of the People's Republic of China are Lycium barbarum polysaccharide (LBP) and betaine. As a result of its structure complexity, only the total level of LBP can be determined, while betaine is not prominent in the pharmacological action of goji and lacks species distinctiveness. Neither of them can well explain the quality of goji. KuA and KuB are commonly used as quality evaluation markers of the Lycii cortex because of their high levels and suitable pharmacological activity. Goji is rich in polyphenols, carotenoids and alkaloids. Many studies have used the above compounds to establish quality evaluation methods but the results have not been satisfactory. Phenolamides have often been neglected in previous studies because of their low single compound levels and high separation difficulty. However, in recent years, the favorable pharmacological activities of phenolamides have been gradually recognized, and studies on goji phenolamides are greatly increasing. In addition, phenolamides have higher species distinctiveness than other compounds and can be combined with other compounds to better evaluate the quality of goji to improve its average quality. CONCLUSIONS: The phenolamides in the goji are rich and play a key role in antioxidation, anti-inflammation, neuroprotection and immunomodulation. As a result of their characteristics, it is suitable to evaluate the quality by quantitative analysis of multi-components by single-marker and fingerprint. This method can be combined with other techniques to improve the quality evaluation system of goji, which lays a foundation for their effectiveness and provides a reference for new quality evaluation methods of similar herbal medicines.

[Cloning and functional analysis of 3ß-hydroxysteroid dehydrogenase gene involved in biosynthesis of digitoxin].

Digitoxin, an important secondary metabolite of Digitalis purpurea, is a commonly used cardiotonic in clinical practice. 3ß-Hydroxysteroid dehydrogenase(3ßHSD) is a key enzyme involved in the biosynthesis of digitoxin. It belongs to the short-chain dehydrogenase/reductase(SDR) family, playing a role in the biosynthesis of cardiac glycosides by oxidizing and isomerizing the precursor sterol. In this study, two 3ßHSD genes were cloned from D. purpurea. The results showed that the open reading frame(ORF) of Dp3ßHSD1 was 780 bp, encoding 259 amino acid residues. The ORF of Dp3ßHSD2 was 774 bp and encoded 257 residues. Dp3ßHSD1/2 had the cofactor binding site TGxxxA/GxG and the catalytic site YxxxK. In vitro experiments confirmed that Dp3ßHSD1/2 catalyzed the generation of progesterone from pregnenolone, and Dp3ßHSD1 had stronger catalytic capacity than Dp3ßHSD2. The expression level of Dp3ßHSD1 was much higher than that of Dp3ßHSD2 in leaves, and digitoxin was only accumulated in leaves. The results implied that Dp3ßHSD1 played a role in the dehydrogenation of pregnenolone to produce progesterone in the biosynthesis of digitoxin. This study provides a reference for further exploring the biosynthetic pathway of cardiac glycosides in D. purpurea.

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.

Sensitive quantitation of ultra-trace toxic aconitines in complex matrices by perfusion nano-electrospray ionization mass spectrometry combined with gas-liquid microextraction.

The accurate analysis of ultra-trace (e.g. <10-4 ng/mL) substances in complex matrices is a burdensome but vital problem in pharmaceutical analysis, with important implications for precise quality control of drugs, discovery of innovative medicines and elucidation of pharmacological mechanisms. Herein, an innovative constant-flow perfusion nano-electrospray ionization (PnESI) technique was developed firstly features significant quantitative advantages in high-sensitivity ambient MS analysis of complex matrix sample. More importantly, double-labeled addition enrichment quantitation strategies of gas-liquid microextraction (GLME) were proposed for the first time, allowing highly selective extraction and enrichment of specific target analytes in a green and ultra-efficient (>1000-fold) manner. Using complex processed Aconitum herbs as example, PnESI-MS directly enabled the qualitative and absolute quantitative analysis of the processed Aconitum extracts and characterized the target toxic diester alkaloids with high sensitivity, high stability, wide linearity range, and strong resistance to matrix interference. Further, GLME device was applied to obtain the highly specific enrichment of the target diester alkaloids more than 1000-fold, and accurate absolute quantitation of trace aconitine, mesaconitine, and hypaconitine in the extracts of Heishunpian, Zhichuanwu and Zhicaowu was accomplished (e.g., 0.098 pg/mL and 0.143 pg/mL), with the quantitation results well below the LODs of aconitines from any analytical instruments available. This study built a systematic strategy for accurate quantitation of ultra-trace substances in complex matrix sample and expected to provide a technological revolution in many fields of pharmaceutical research.

IMP: bridging the gap for medicinal plant genomics.

Medicinal plants have garnered significant attention in ethnomedicine and traditional medicine due to their potential antitumor, anti-inflammatory and antioxidant properties. Recent advancements in genome sequencing and synthetic biology have revitalized interest in natural products. Despite the availability of sequenced genomes and transcriptomes of these plants, the absence of publicly accessible gene annotations and tabular formatted gene expression data has hindered their effective utilization. To address this pressing issue, we have developed IMP (Integrated Medicinal Plantomics), a freely accessible platform at https://www.bic.ac.cn/IMP. IMP curated a total of 8 565 672 genes for 84 high-quality genome assemblies, and 2156 transcriptome sequencing samples encompassing various organs, tissues, developmental stages and stimulations. With the integrated 10 analysis modules, users could simply examine gene annotations, sequences, functions, distributions and expressions in IMP in a one-stop mode. We firmly believe that IMP will play a vital role in enhancing the understanding of molecular metabolic pathways in medicinal plants or plants with medicinal benefits, thereby driving advancements in synthetic biology, and facilitating the exploration of natural sources for valuable chemical constituents like drug discovery and drug production.

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.

[Research progress in tigliane-type macrocyclic diterpenoids].

Tigliane type macrocyclic diterpenoids with special structures and diverse bioactivities are mainly extracted from plants of Euphorbiaceae and Thymelaeaceae. According to the different functional groups, they can be classified into types of phorbol esters, C-4 deoxyphorbol esters, C-12 deoxyphorbol esters, C-16 or C-17 substituted phorbol esters and others. Most of them present promising antiviral activities and cytotoxic activities and are expected to be developed as candidates for anti-AIDS, anti-tuberculosis, and anti-tumor clinical trials, demonstrating great potential for the application in healthcare. This paper reviews 115 novel tigliane-type diterpenoids discovered since 2013 and summarize their chemical structures and bioactivities, aiming to lay a foundation for further development and utilization of these compounds and provide new ideas for the development of clinical drugs.

Potential benefits of Rehmanniae Radix after ancient rice-steaming process in promotion of antioxidant activity in rats' health.

Rice steam processed product of Rehmanniae Radix (RSRR), one of the processed products of Rehmanniae Radix (RR), is popular as an herbal medicine and food. However, the health-promoting effects and mechanisms of RSRR are still unclear. In this study, 10-week-old Sprague-Dawley female rats were treated with different processed products of RR. No organ coefficient differences were observed between RSRR and the control group, indicating that RSRR did not cause damage to the rats. Compared with other RR products, superoxide dismutase, glutathione, and catalase levels were significantly higher and malondialdehyde levels were significantly lower in the RSRR group, indicating that RSRR exerted a better antioxidant effect. Gene expression analysis showed that hemoglobin genes (Hba-a1, Hba-a2, Hbb-bs, Hbb, Hbq1b, Hbb-b1, and LOC103694857) may be potential biomarkers to evaluate the antioxidant effect of RSRR. Antioxidation-related signaling pathways in GO annotation, including cellular oxidant detoxification, hydrogen peroxide metabolic process, hemoglobin complex, and oxygen binding signaling pathways were significantly enriched, indicating these pathways may represent the antioxidant mechanism of RSRR. To explore the main active compounds primarily responsible for the antioxidant activity of RSRR, UPLC-Q-TOF-MS was used and six components (catalpol, rehmannioside A, rehmannioside D, melittoside, ajugol, and verbascoside) were identified in rat serum. Catalpol and rehmannioside A were predicted to be the major active components by network pharmacology. These results suggested that RSRR exhibits antioxidant activity and has health-promoting properties. This study provides a scientific basis for the antioxidant mechanism and clinical use of RSRR.

[Advances on the microbial synthesis of plant-derived diterpenoids].

Natural plant-derived diterpenoids are a class of compounds with diverse structures and functions. These compounds are widely used in pharmaceuticals, cosmetics and food additives industries because of their pharmacological properties such as anticancer, anti-inflammatory and antibacterial activities. In recent years, with the gradual discovery of functional genes in the biosynthetic pathway of plant-derived diterpenoids and the development of synthetic biotechnology, great efforts have been made to construct a variety of diterpenoid microbial cell factories through metabolic engineering and synthetic biology, resulting in gram-level production of many compounds. This article summarizes the construction of plant-derived diterpenoid microbial cell factories through synthetic biotechnology, followed by introducing the metabolic engineering strategies applied to improve plant-derived diterpenoids production, with the aim to provide a reference for the construction of high-yield plant-derived diterpenoid microbial cell factories and the industrial production of diterpenoids.

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.

Alashanines A-C, Three Quinone-Terpenoid Alkaloids from Syringa pinnatifolia with Cytotoxic Potential by Activation of ERK.

Three quinone-terpenoid alkaloids, alashanines A-C (1-3), possessing an unprecedented 6/6/6 tricyclic conjugated backbone and quinone-quinoline-fused characteristic, were isolated from the peeled stems of Syringa pinnatifolia. Their structures were elucidated by analysis of extensive spectroscopic data and quantum chemical calculations. A hypothesis of biosynthesis pathways for 1-3 was proposed on the basis of the potential precursor iridoid and benzoquinone. Compound 1 exhibited antibacterial activities against Bacillus subtilis and cytotoxicity against HepG2 and MCF-7 human cancer cell lines. The results of the cytotoxic mechanism revealed that compound 1 induced apoptosis of HepG2 cells through activation of ERK.

PuCRZ1, an C2H2 transcription factor from Polyporus umbellatus, positively regulates mycelium response to osmotic stress.

Polyporus umbellatus is an edible and medicinal mushroom with the capacity to produce sclerotia. However, the mechanism of P. umbellatus sclerotia formation is unclear. CRZ1 is a C2H2 family transcription factor involved in the Ca2+-calcineurin signaling pathway, which has the function of regulating sclerotia formation, maintaining ion homeostasis, and responding to stress. In this study, we identified 28 C2H2 transcription factors in P. umbellatus genome, 13 of which are differentially expressed between mycelium and sclerotia, including PuCRZ1. Combining DNA affinity purification and sequencing (DAP-seq) and quantitative real-time PCR (qRT-PCR), three genes (PuG10, PuG11, PuG12) were identified as putative PuCRZ1 target genes containing a putative binding motif (GTGGCG) within their promoter. Yeast single hybridization (Y1H) and EMSA further confirmed that PuCRZ1 can bind to the promoter region of PuG10, PuG11, and PuG12. PuCRZ1 gene could reduce the sensitivity of NaCl in yeast cells. Furthermore, overexpression of the PuCRZ1 target gene, especially the FVLY domain containing gene PuG11, could improve the mycelia growth rate and mannitol tolerance in P. umbellatus. These results demonstrate that PuCRZ1 in the Ca2+-calcineurin signaling pathway plays an important role in mycelia growth, as well as osmotic stress tolerance.

Discovery of YH677 as a cancer stemness inhibitor that suppresses triple-negative breast cancer growth and metastasis by regulating the TGFß signaling pathway.

Triple-negative breast cancer (TNBC) has a poor prognosis due to the lack of specific and highly effective therapeutic agents. Cancer stem cells (CSCs) are one of the main factors contributing to TNBC relapse and metastasis. Therefore, targeting CSCs selectively with small molecules is a novel strategy for drug development. In this study, the natural product harmine (HM) was identified as a hit compound from 2632 natural product monomers based on phenotypic screening of a 2D assay and patient-derived organoid (PDO) model that was established from a patient who had multiple drug resistance and various visceral and contralateral breast metastases. Next, harmine was further modified and optimized to obtain a lead compound (YH677) with a tetrahydro-ß-carboline scaffold. YH677 showed potent antiproliferative and antimigratory activities against several TNBC cell lines in vitro. In addition, YH677 inhibited epithelial mesenchymal transition (EMT) and stem cell marker expression in a dose-dependent manner. More importantly, YH677 suppressed breast cancer growth and metastasis in orthotopic, metastatic xenograft and patient-derived xenograft (PDX) models in vivo. Mechanistic studies showed that YH677 inhibits the expansion of CSCs by regulating the TGFß/Smad signaling pathway. These preclinical data provide a basis for the development of YH677 as a lead compound for TNBC treatment.

Tandemly duplicated CYP82Ds catalyze 14-hydroxylation in triptolide biosynthesis and precursor production in Saccharomyces cerevisiae.

Triptolide is a valuable multipotent antitumor diterpenoid in Tripterygium wilfordii, and its C-14 hydroxyl group is often selected for modification to enhance both the bioavailability and antitumor efficacy. However, the mechanism for 14-hydroxylation formation remains unknown. Here, we discover 133 kb of tandem duplicated CYP82Ds encoding 11 genes on chromosome 12 and characterize CYP82D274 and CYP82D263 as 14-hydroxylases that catalyze the metabolic grid in triptolide biosynthesis. The two CYP82Ds catalyze the aromatization of miltiradiene, which has been repeatedly reported to be a spontaneous process. In vivo assays and evaluations of the kinetic parameters of CYP82Ds indicate the most significant affinity to dehydroabietic acid among multiple intermediates. The precursor 14-hydroxy-dehydroabietic acid is successfully produced by engineered Saccharomyces cerevisiae. Our study provides genetic elements for further elucidation of the downstream biosynthetic pathways and heterologous production of triptolide and of the currently intractable biosynthesis of other 14-hydroxyl labdane-type secondary metabolites.

Transcriptional regulatory network of high-value active ingredients in medicinal plants.

High-value active ingredients in medicinal plants have attracted research attention because of their benefits for human health, such as the antimalarial artemisinin, anticardiovascular disease tanshinones, and anticancer Taxol and vinblastine. Here, we review how hormones and environmental factors promote the accumulation of active ingredients, thereby providing a strategy to produce high-value drugs at a low cost. Focusing on major hormone signaling events and environmental factors, we review the transcriptional regulatory network mediating biosynthesis of representative active ingredients. In this network, many transcription factors (TFs) simultaneously control multiple synthase genes; thus, understanding the molecular mechanisms affecting transcriptional regulation of active ingredients will be crucial to developing new breeding possibilities.

Huashibaidu formula attenuates sepsis-induced acute lung injury via suppressing cytokine storm: Implications for treatment of COVID-19.

BACKGROUND: Acute lung injury (ALI) is a common complication of sepsis with poor effective interventions. Huashibaidu formula (HSBD) showed good therapeutic effects in treating coronavirus disease 2019 (COVID-19) patients. PURPOSE: This study was designed to investigate the therapeutic potential and precise mechanism of HSBD against sepsis-induced ALI based on network pharmacology and animal experiments. MATERIALS AND METHODS: Network pharmacology was used to predict the possible mechanism of HSBD against sepsis. Next, a sepsis-induced ALI rat model via intraperitoneal lipopolysaccharide (LPS) was constructed to evaluate the level of inflammatory cytokines and the degree of lung injury. The expression of inflammation-related signaling pathways, including TLR4/NF-κB and PI3K/Akt was determined by western blot. RESULTS: Network pharmacology analysis indicated that HSBD might have a therapeutic effect on sepsis mainly by affecting inflammatory and immune responses. Animal experiments demonstrated that HSBD protected the lung tissue from LPS-induced injury, and inhibited the levels of inflammatory cytokines such as interleukin (IL)-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the serum and IL-1ß, IL-5, IL-6, IL-18, GM-CSF, IFN-γ and TNF-α in the lung tissue. Western blot results revealed that HSBD downregulated the expression of TLR4/NF-κB and upregulated the expression of PI3K/Akt. CONCLUSION: The therapeutic mechanism of HSBD against sepsis-induced ALI mainly involved suppressing cytokine storms and relieving inflammatory symptoms by regulating the expression of TLR4/NF-κB and PI3K/Akt. Our study provides a scientific basis for the mechanistic investigation and clinical application of HSBD in the treatment of sepsis and COVID-19.

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.