Aberrant Gut Microbiome Contributes to Barrier Dysfunction, Inflammation, and Local Immune Responses in IgA Nephropathy.

INTRODUCTION: Numerous research works have shown that serum Gal-deficient (Gd) IgA1 levels are increased in IgA nephropathy (IgAN) patients and these levels are a dangerous risk factor for IgAN. A relationship between the gut microbiota and IgAN has been reported. Whether the gut microbiota participates in the pathogenesis of IgAN was still controversial. METHODS: We evaluated changes in the gut flora and the levels of Gd-IgA1 in IgAN patients and healthy controls (HCs). We investigated the Gd-IgA1 levels in both blood and urine specimens. C57BL/6 mice were given a broad-spectrum antibiotic cocktail to deplete the endogenous gut flora. We established a model of IgAN in pseudosterile mice and investigated the expression of the markers of intestinal permeability, inflammation, and local immune responses. RESULTS: Studies have shown that the levels of certain gut flora differ between IgAN patients and HCs. Moreover, elevated Gd-IgA1 levels were found in both the serum and urine. Interestingly, Coprococcus, Dorea, Bifidobacterium, Blautia, and Lactococcus, selected from 10 candidate biomarkers to predict risk in IgAN patients according to random forest analysis, were inversely associated with urinary Gd-IgA1 levels. Notably, the urine level of Gd-IgA1 could best distinguish IgAN patients from HCs. Additionally, the degree of kidney damage in pseudosterile mice with IgAN was more severe than that in mice with IgAN. Furthermore, the markers of intestinal permeability were significantly elevated in pseudosterile IgAN mice. Moreover, the inflammation responses (TLR4, MyD88, and NF-κB in intestinal and renal tissues; TNF-α and IL-6 in serum) and local immune responses (BAFF and APRIL in intestinal tissue) were upregulated in pseudosterile IgAN mice. CONCLUSIONS: The urine Gd-IgA1 level may be as a biomarker for the early screening of potential IgAN, and gut microbiota dysbiosis was demonstrated in IgAN, which might involve the dysfunction of the mucosal barrier, inflammation, and local immune responses.

Microwave-Assisted Enzymatic Extraction, Partial Characterization, and Antioxidant Potential of Polysaccharides from Sagittaria trifolia Tuber.

Sagittaria trifolia tuber is an aquatic vegetable. In this work, microwave-assisted enzymatic extraction (MEE) was used to extract S. trifolia tuber polysaccharides (STTPs). Optimum conditions were complex enzyme of 2 %, liquid-to-solid ratio of 43 : 1 mL g-1 , microwave power of 506 W, and time of 8 min, under which STTPs yield was 36.22±0.69 %, higher than those of other methods. STTPs were sulfated polysaccharides with sulfur valence of S6+ . STTPs comprised mannose, glucose, galactose, and arabinose at a mole ratio of 3.69 : 19.33 : 6.21 : 1.00, molecular weights of 3606 kDa and 149.6 kDa, particle size of 220 nm, and zeta potential of -5.02 mV. The surface of STTPs was full of bumps and holes, and abundant in O1s and non-functionalized C1s. STTPs would scavenge reactive oxygen species with advantage. It would provide an efficient MEE method to obtain antioxidant STTPs, also a clue for extracting polysaccharides from starch-rich crops.

Eleocharis dulcis corm: phytochemicals, health benefits, processing and food products.

Eleocharis dulcis, an aquatic plant belonging to Cyperaceae family, is indigenous to Asia, and also occurs in tropical Africa and Australia. The edible corm part of E. dulcis is a commonly consumed aquatic vegetable with a planting area of 44.46 × 103 hm2 in China. This work aims to explore the potential of E. dulcis corm for use as a new food source for sufficient nutrients and health benefits by reviewing its nutrients, phytochemicals, functions, processing and food products. Eleocharis dulcis corm contains starches, dietary fibers, non-starch polysaccharides, proteins, amino acids, phenolics, sterols, puchiin, saponins, minerals and vitamins. Among them, phenolics including flavonoids and quinones could be the major bioconstituents that largely contribute to antioxidant, anti-inflammatory, antibacterial, antitumor, hepatoprotective, neuroprotective and hypolipidemic functions. Peel wastes of E. dulcis corm tend to be enriched in phenolics to a much higher extent than the edible pulp. Fresh-cut E. dulcis corm can be consumed as a ready-to-eat food or processed into juice for beverage production, and anti-browning processing is a key to prolonging shelf life. Present food products of E. dulcis corm are centered on various fruit and vegetable beverages, and suffer from single categories and inadequate development. In brief, underutilized E. dulcis corm possesses great potential for use as a new food source for sufficient nutrients and health benefits. © 2021 Society of Chemical Industry.

The ester derivatives obtained by C-ring modification of podophyllotoxin induce apoptosis and inhibited proliferation in PC-3M cells via down-regulation of PI3K/Akt signaling pathway.

Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially its anti-tumor effects. To improve the cytotoxicity and selective effect of PPT, in this study, we have designed and synthesized 20 ester derivatives by introducing Boc-amino acids or organic acids at the C-4 position of PPT. The cytotoxicity of these compounds was evaluated with PC-3M, HemECs, A549, MCF-7 and HepG2 cells. We observed that the proliferation of PC-3M cells was inhibited by all 20 ester derivatives in the largest degree, comparing to the other cell lines. Comparing to PPT (IC50 = 234.90 ± 20.7 nM), eight derivatives had better performance in inhabiting proliferation of PC-3M cells, six of them belong to Boc-amino acid ester derivatives, and the derivative named V-05 (IC50 = 1.28 ± 0.1 nM) had the strongest inhibitation effect. Changes in cell proliferation and apoptotic signaling pathways were studied by DAPI staining, colony formation assay, migration assay, flow cytometry and western blot analysis. We found that V-05 were able to inhibit PC-3M cells proliferation and migration, and induced apoptosis by downregualting p-PI3K, p-Akt and Bcl-2, and upregulating Cleaved caspase-3 and Bax. Our research provides the first insight for the application of PPT derivatives in PC-3M cells, which may offer information to the effective medicine development for human prostate cancer treatment.

Protective Effects of Ginsenosides (20R)-Rg3 on H2 O2 -Induced Myocardial Cell Injury by Activating Keap-1/Nrf2/HO-1 Signaling Pathway.

Ginsenosides (20S)-Rg3 and (20R)-Rg3 are famous rare ginsenosides from red ginseng, and their configurations in C-20 are different. This study aimed to investigate the protective mechanism of ginsenosides (20S)-Rg3 and (20R)-Rg3 on H2 O2 -induced H9C2 cells and compare their activity. The results showed that the ginsenosides (20S)-Rg3 and (20R)-Rg3 could increase the cell activity and the levels of GSH-Px, SOD and CAT, and decrease activities of LDH, MDA and ROS. Further studies showed that ginsenosides (20S)-Rg3 and (20R)-Rg3 could prevent oxidative stress injury of H9C2 cells by H2 O2 through the Keap-1/Nrf2/HO-1 pathway. But the ML385 counteracts these effects. Interestingly, among these results, ginsenoside (20R)-Rg3 was superior to (20S)-Rg3, indicating that ginsenoside (20R)-Rg3 have a stronger effect of antioxidative stress. This study reflected that ginsenoside (20R)-Rg3 could be used as a potential Nrf2 activator and a safe effective Chinese herbal monomer in the treatment of cardiovascular disease.

Potential Myocardial Protection of 3,4-seco-Lupane Triterpenoids from Acanthopanax sessiliflorus Leaves.

A rich of 3,4-seco-lupane triterpenoids including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA) and chiisanogenin (CSG) were isolated from the ethanol extract of the leaves of Acanthopanax sessiliflorus. On the basis of previous studies, this article focused on four important components of 3,4-seco-lupane triterpenoids in Acanthopanax sessiliflorus leaves and explored their protective effects against aconitine-induced cardiomyocyte injury and their molecular mechanisms. The results showed that pretreatment with 3,4-seco-lupane triterpenoids could effectively increase cell viability, reduce CK-MB and LDH activities, reduce ROS production, maintain calcium concentration balance, and inhibit apoptosis, with divaroside having the best effect. In addition, Western blot results showed that divaroside down-regulated Cleaved caspase-3 and Bax and up-regulated Bcl-2 expression through activating the PI3 K/AKT pathway. However, the LY294002 inhibitor reversed this situation. This suggests that 3,4-seco-lupane triterpenoids may be a new hotspot for potential myocardial protective drugs research.

Sagittaria trifolia tuber: bioconstituents, processing, products, and health benefits.

Sagittaria trifolia is an aquatic plant that is distributed worldwide. The edible tuber part of S. trifolia is a very common and popular vegetable in China. The aim of the present review is to discuss the discovery of nutraceuticals from S. trifolia tuber by reviewing its major constituents, food processing, food products, and health-promoting benefits. Sagittaria trifolia tuber comprises a series of nutritional and bioactive constituents, including dietary fibers, amino acids, minerals, starches, non-starch polysaccharides, diterpenoids, colchicine, phenols, and organic acids. Food processing affects its flavor, biocomponents, and bioactivity. Numerous S. trifolia tuber-based food products and nutraceuticals have been developed, but new categories of products and the anticipated functions still need to be explored. The non-starch polysaccharides could be the central ingredients that contribute to the plant's antioxidant, hepatoprotective, hypoglycemic, lipid-regulating, and immunostimulatory properties. Of these, antioxidant and hepatoprotective effects have been thoroughly investigated. Procedures for the extraction and purification of polysaccharides influence their health-promoting actions. Overall, S. trifolia tuber is an underutilized aquatic vegetable species that is an emerging subject for nutraceutical research. © 2020 Society of Chemical Industry.

The structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47.

OBJECTIVES: To study the structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47, and to provide an easier template for R&D of RhoA inhibitor. RESULTS: Our initial attempts to obtain a binary complex of RhoA with the inhibitor HL47 were unsuccessful probably due to the presence of GDP. By targeting a ternary complex involving the RhoA-specific guanine nucleotide exchange factor PDZRhoGEF, we eliminated GDP and obtained a 2.3 Å structure of the RhoA-PDZRhoGEF-inhibitor HL47 ternary complex. CONCLUSION: This structure provides a new template for target-based pharmaceutical design against RhoA.

MiR-204 enhances the progression of osteoarthritis by suppressing the production of IL-1ß.

Recent studies suggest that cytokines and microRNAs play a key role in the destruction of cartilage matrix in osteoarthritis (OA) tissues. In the current study, we focused on miR-204, which has never been explored in OA. We found that the level of miR-204 was markedly reduced in the OA cartilage tissues compared with that of normal control. Real time PCR analysis demonstrated that the level of miR-204 was markedly decreased after IL-1ß treatment for 3, 6, 12 h in the normal chondrocytes and OA chondrocytes, respectively. Furthermore, overexpression of miR-204 markedly suppressed the protein levels of IL-1ß, COX-2 and IL6 in human OA chondrocytes and chondrogenic SW1353 cells. Dual luciferase reporter assay demonstrated that miR-204 significantly suppressed the relative luciferase activity of pmirGLO-IL-1ß-3'UTR, indicating that IL-1ß was a target gene of miR-204. More importantly, treatment with IL-1ß significantly enhanced the protein levels of IL-1ß, COX-2 and IL6. However, overexpression of miR-204 could partially abolish such effects. In conclusion, our data demonstrate that reduced miR-204 expression enhances the destruction of the cartilage tissues among OA patients mainly through targeting IL-1ß.

Therapeutic Effect of Chenodeoxycholic Acid in an Experimental Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile. However, the therapeutic effect of CDCA on OA severity was largely unknown. The purpose of this study was to evaluate the therapeutic effect of intra-articular injection of CDCA in a rabbit OA model. OA was induced in experimental rabbits by anterior cruciate ligament transection (ACLT) and then rabbits were intra-articularly injected with CDCA (10 mg/kg or 50 mg/kg) once per week for 5 weeks. The results showed that CDCA significantly decreased cartilage degradation on the surface of femoral condyles, reducing the pathological changes of articular cartilage and synovial membrane by macroscopic and histological analysis. CDCA also significantly decreased bone destruction and erosion of joint evaluated by micro-CT. Furthermore, CDCA could markedly reduce the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2) in synovial fluid. These observations highlight CDCA might be a potential therapeutic agent for OA.

Biomimetic exosomal vesicles loaded with siRNA improves antitumor immune responses by inhibiting the secretion of tumor-derived exosome PD-L1.

Tumor-derived exosome PD-L1 exhaustsTcells and permits tumor cells to evade immune surveillance; thus, the inhibition of ExoPD-L1 secretion can significantly enhance the clinical efficacy of PD-L1 antibody. In this study, we combined exosome membrane, apoA1 and phospholipid into biomimetic exosome vesicles (apoA1-bExo) which were then incubated with cholesterol modified siRNA to generate apoA1-bExo containing siRNA (apoA1-bExo/siRNA). Thepreparedvesicleswere uniformandsphericalin size and could be loaded effectively with siRNA to protect from nuclease degradation. Compared with bExo/siRNA, apoA1-bExo/siRNA showed stronger tumor targeting, tissue permeability, intracellular accumulation efficiency and antitumor efficiency. A portion of apoA1-bExo/siRNA transport siRNA occurred through the endosome-Golgi-ER pathway similar to bExo/siRNA, but mostly occurred directly through selective uptake pathways mediated by the SR-B1 receptor. apoA1-bExo/siRNA successfully achieved silencing efficiency at the transcription and protein levels (96.78 % and 94.07 %, respectively) and reduced the secretion of ExoPD-L1 from HepG2 cells to 15.92 % of that in the PBS group, thus enhancing the killing activity of co-cultured T cells on HepG2 cells. In addition, relevant pharmacodynamic indices were positively correlated with delivery efficiency and the modification of apoA1 could significantly enhance the intracellular accumulation of siRNA, thus exhibiting stronger activity than bExo/siRNA. Moreover, in addition to curing mice of their implanted tumors, blocking ExoPD-L1 secretion in combination with αPD-1 promoted the infiltration of durable antitumor hCD8+ T cells and hCD45+ T cells into tumor in a immune system-tumor dual humanized mice.

Enzymatic synthesis of Vaccinium blue using vaccinoside as a bifunctional precursor.

Since Tang dynasty in China, the fresh leaves of Vaccinium bracteatum (VBL) have been applied as natural pigment to produce black rice. However, detailed information on its biosynthetic mechanism still remained unclear. Following rice dyeing capacity assay, vaccinoside, one of iridoid glycosides, was identified as the key active compound. Increased methodical research demonstrated vaccinoside as a distinct bifunctional precursor, which could be catalyzed by polyphenol oxidase or ß-glucosidase independently, followed by reaction with 15 amino acids to give blue pigments (VBPs; λmax 581-590 nm) of different hues. Two synthetic pathways of VBPs were proposed, using multiple techniques such as HPLC, HPSEC, UV-Vis spectrum and colorimeter as analysis tools. Black rice was interpreted to be prepared by cooking, using vaccinoside, intrinsic enzymes from fresh VBL and rice protein in combination. These findings promote the understanding of VBP formation mechanisms and provide an efficient method of producing novel Vaccinium blue pigments.

Isotoosendanin exerts anti-tumor effects in NSCLC by enhancing the stability of SHP-2 and inhibiting the JAK/STAT3 pathway.

BACKGROUND: Lung cancer has been considered as a serious problem for the public health system. NSCLC is the main type of lung cancer, and finding improved treatments for NSCLC is a pressing concern. In this study, we have explored the efficacy of isotoosendanin (ITSN) for the treatment of NSCLC, and also explored the potential underlying mechanisms. METHODS: NSCLC cells were cultured, and colony formation, cell cycle as well as apoptosis assays have been conducted for investigating the biological functions of ITSN on NSCLC cells. Furthermore, target genes of ITSN have been predicted via PharmMapper and SuperPred database, subsequently validated using the drug affinity responsive target stability (DARTS) approach, a cellular thermal shift assay (CETSA) as well as surface plasmon resonance (SPR) analysis. Additionally, ubiquitination experiments have been conducted for the level of ubiquitination of the NSCLC cells. Finally, a nude mouse xenograft model has been established for evaluating the anti-tumor effects of ITSN in vivo. RESULTS: ITSN has shown anti-NSCLC activities both in vitro and in vivo. Mechanistically, ITSN interacts with SHP-2 through enhancing its stability and decreases the level of ubiquitination. Notably, ITSN may regulate the behaviors of NSCLC cells via affecting the JAK/STAT3 signaling, and finally, the anti-tumor effects of ITSN was partially reversed by the application of SHP-2 inhibitor or siRNA of SHP-2. CONCLUSIONS: ITSN may exert its anti-tumor effects by directly targeting SHP-2, increasing its stability and minimizing its ubiquitination. These results imply that ITSN could be a revolutionary component for treating NSCLC.

Intermittent aeration to reduce gaseous emission and advance humification in food waste digestate composting: Performance and mechanisms.

This study investigated the performance and mechanisms of intermittent aeration to regulate gaseous emission and humification during food waste digestate composting. In addition to continuous aeration, three intermittent aeration regimes were conducted with the on-off interval ratio at 3:1, 2:1, and 1:1 within each 30 min, respectively. Results showed that intermittent aeration regimes reduced gaseous emission and enhanced humification during composting. In particular, intermittent aeration with the on/off ratio of 1:1 was more effective to reduce organic mineralization than other regimes, which alleviated the emission of nitrous oxide and ammonia by 63.1% and 75.7% in comparison with continuous aeration, respectively. In addition, this aeration regime also enhanced the content of humic acid by 24.1%. Further analysis demonstrated that prolonging aeration-off intervals could enrich facultative bacteria (e.g. Atopobium and Clostridium) from digestate and inhibit the proliferation of several aerobic bacteria (e.g. Caldicoprobacter and Marinimicrobium) to retard organic mineralization for humification.

Microwave-assisted enzymatic extraction brings a notably high yield of polysaccharides from mountain Zizania latifolia.

Mountain Zizania latifolia is produced at scale in China, and the edible swollen culm is exported to many countries, but little attention has been paid to its functional components. In this work, microwave-assisted enzymatic extraction (MAEE) is used for the first time to extract polysaccharides from mountain Z. latifolia swollen culm (PMZL). MAEE conditions optimized by Box-Behnken design-response surface methodology were as follows: 2.4% cellulase, microwaving for 6.0 min at 607 W, with a liquid-to-solid ratio of 63:1 ml g-1 . Under these conditions, a notably high yield of 60.43% ± 1.12% for PMZL was achieved, which was significantly higher (p < 0.01) than from plain-grown varieties. PMZL are naturally occurring sulfated polysaccharide-protein complexes containing 8.46% ± 0.18% proteins and 7.86% ± 0.73% sulfates. PMZL comprises mannose, glucosamine, rhamnose, glucose, galactose, and arabinose at molar ratios of 3.80:2.68:1.00:17.41:5.12:2.91, with a weight-average molecular weight of 1569,219 Da and a number-average molecular weight of 364,088 Da. The surface morphology of PMZL is composed of tightly packed oval particles, and this kind of promising polysaccharides preferentially scavenges reactive nitrogen species. PRACTICAL APPLICATION: Due to global warming, the land available for planting vegetables is likely to expand to higher areas, so greater attention should now be paid to mountain-grown vegetables. This study provides an efficient way to obtain novel polysaccharides from mountain Zizania latifolia using microwave-assisted enzymatic extraction with a remarkably high yield of 60.4%. This promising source of natural carbohydrates has potential uses in pharmaceutical, nutraceutical, functional foods, cosmetics, and functional materials industries.

ASPS Exhibits Anti-Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ-Glutamylcysteine Level.

Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen-induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC-MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ-glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production.

Therapeutic effect of leflunomide on the development of experimental lupus nephritis in mice.

Mice with chronic graft-versus-host disease (cGVHD) induced by transferring parental BALB/C lymphocytes into (C57BL/6 × BALB/C) F1 (CBF1) hybrids, develop a syndrome characterized by B-cell hyperactivity, autoantibody production, and immune complex-mediated glomerulonephritis. In this model, we evaluated the role of leflunomide on the development of lupus nephritis in system autoimmunity. Daily administration of leflunomide (15 mg/kg/d) from 2 weeks after cGVHD induction can dramatically reduce the production of autoantibodies and immune complex deposition in the kidney, leading to relieved kidney damage and reduced mortality. The therapeutic effect of leflunomide on the lupus-prone mice was partially due to the inhibition of TLR9 signaling pathway, which was an important component of innate immune system.

Cytotoxic and anti-tumor effects of 3,4-seco-lupane triterpenoids from the leaves of Eleutherococcus sessiliflorus against hepatocellular carcinoma.

A rich of 3,4-seco-lupane triterpenoids (3,4-SLT), including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA), chiisanogenin (CSG), sessiligenin (SSG), were isolated from the ethanol extract of the leaves of Eleutherococcus sessiliflorus (LES). The present study was performed to explore the cytotoxic and anti-tumor effects of the isolated five ones, as well as potential molecular mechanisms. The results of a CCK-8 assay demonstrated that these 3,4-SLT can inhibit the growth of HepG2 cells, and SSG showed the most significant cytotoxicity. Hoechst 33258 fluorescence staining and Annexin V-FITC/PI staining indicated that 3,4-SLT in LES can induce HepG2 cell apoptosis effectively. The AutoDock Vina program was used to simulate molecular docking of drugs and targets to discuss possible pharmacological mechanisms. Besides, western blot and qRT-PCR results indicated that SSG can inhibit PI3K/AKT signaling pathway through controlling multi-targets. This study suggested that 3,4-SLT might become a new research hotspot for antineoplastic drugs.

Humification and maturation of kitchen waste during indoor composting by individual households.

This study evaluated the humification and maturation of kitchen waste during indoor composting by individual households. In total, 50 households were randomly selected to participate in this study using kitchen waste of their own for indoor composting using a standard 20 L sealed composter. Garden waste was also collected from their local communities and used as the bulking agent. Both effective microorganisms and lime were inoculated at 1% (wet weight) of raw composting materials to facilitate the composting initiation. Results from this study demonstrate for the first time that ordinary residents could correctly follow the instruction to operate indoor composting at household level to manage urban kitchen waste at source. Overall, 30 households provided valid and complete data to show an increase (to ~50 °C) and then decrease in temperature in response to the decline of biodegradable organic substances during indoor composting. The compost physiochemical characteristics varied significantly toward maturation with an increase in seed germination index to above 50% for most households. Furthermore, organic humification occurred continuously during indoor composting as indicated by the enhanced content of humic substances, degree of polymerization, and spectroscopic characteristics.

The ester derivatives obtained by C-ring modification of podophyllotoxin-induced apoptosis and inhibited proliferation in Hemangioma Endothelial Cells via downregulation of PI3K/Akt signaling pathway.

Infantile hemangioma (IH) is a common benign endothelial cell tumor in infants and young children, sometimes accompanied by potential complications, and may develop into malignant tumors. Hemangioma endothelial cells (HemECs) are one of the main components of IH. Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially anti-tumor, but its high toxicity, poor water solubility, and serious gastrointestinal side effects limit its clinical application. In this study, we have designed and synthesized 20 ester derivatives by introducing Boc-amino acids or organic acids at the C-4 position of podophyllotoxin through esterification reactions. The cytotoxicity of these compounds was evaluated on HemECs. Changes in cell proliferation and apoptotic signaling pathways were studied by DAPI staining, colony formation assay, migration assay, measurement of reactive oxygen species (ROS) levels flow cytometry, and Western blot analysis. We found that eight of the compounds were more potent than PPT. Of these, compound V-31 was the most active (IC50  = 0.079 ± 0.0049 µM). Further research indicated that compound V-31 inhibited its proliferation and migration, increased the level of ROS in cells, and induced apoptosis by downregulating p-PI3K, p-Akt, and Bcl-2, and upregulating cleaved caspase-3 and Bax. Our research provides the first insight into the application of PPT derivatives in HemECs, may provide an effective medicine for IH treatment.