Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previo...Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work demonstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P<0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P<0.05).This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-PKA-CREB signaling pathway(P<0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P<0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.展开更多
Oleanolic acid(OA),a pentacyclic triterpenoid,exhibits a broad spectrum of biological activities,including antitumor,antiviral,antibacterial,anti-inflammatory,hepatoprotective,hypoglycemic,and hypolipidemic effects.Si...Oleanolic acid(OA),a pentacyclic triterpenoid,exhibits a broad spectrum of biological activities,including antitumor,antiviral,antibacterial,anti-inflammatory,hepatoprotective,hypoglycemic,and hypolipidemic effects.Since its initial isolation and identification,numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives.Despite this,there has been a dearth of comprehensive reviews in the past two decades,leading to challenges in subsequent research on OA.Based on the main biological activities of OA,this paper comprehensively summarized the modification strategies and structureactivity relationships(SARs)of OA and its derivatives to provide valuable reference for future investigations into OA.展开更多
Oleanolic acid(OA)and ursolic acid(UA)are commonly present in the cuticular wax of many edible fruits and medicinal herbs.OA and UA belong to the group of bioactive pentacyclic triterpenoids,exhibiting a wide range of...Oleanolic acid(OA)and ursolic acid(UA)are commonly present in the cuticular wax of many edible fruits and medicinal herbs.OA and UA belong to the group of bioactive pentacyclic triterpenoids,exhibiting a wide range of beneficial effects including protection for the kidneys,liver,heart,gastrointestinal tract,and spinal cord.Additionally,OA and UA exhibit antioxidant,anti-ferroptotic,anti-apoptotic,anti-inflammatory,anti-tumor,anti-viral,anti-diabetic,anti-microbial,anti-parasitic,analgesic,wound-healing,hypolipidemic,and hypoglycemic properties,often without notable side effects.Due to the extensive array of their positive functions,it is not feasible to thoroughly cover all aspects in this review.Therefore,the primary focus lies on reviewing the natural sources,extraction,and nephroprotective properties of OA and UA.To summarize,current literatures highlight the nephroprotective mechanisms of OA and UA,primarily involving inhibiting oxidative stress,endoplasmic reticulum stress,glycative stress,dyslipidemia,inflammation,apoptosis,pyroptosis,and renal fibrosis,promoting diuresis,as well as fine-tuning autophagy.展开更多
Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal herbs.Conversely,the OA that...Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal herbs.Conversely,the OA that impacts colon cancer(CC)cells and its underlying mechanisms remain poorly understood.Methods:The cytotoxic effect of OA alone or OA-5-Fluorouracil(5-FU)combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide(MTT).Then,the impact of OA on CC cell lines(LoVo and HT-29)proliferation and stemness were measured using colon formation and tumorsphere formation assays.Octamer-binding transcription factor 4(Oct4),Prominin-1(CD133),Nanog,and transcription factor SOX-2(SOX2)are cell stemness-related indicators whose expression was assessed usingfluorescence qPCR assay,Western blotting,and immunohistochemistry.The effect of OA on the proliferative potency of CC cells was evaluated using an in vivo model.Results:The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU.Moreover,OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers(CD133,Nanog,SOX2,and Oct4)expression levels both in vitro and in vivo,as well as by inactivating the activator of transcription 3(STAT3 signaling)and Janus kinase 2/signal transducer(JAK2).Conclusion:Thesefindings imply that oleanolic acid,both in vitro and in vivo,suppresses the JAK2/STAT3 pathway,which in turn reverses chemoresistance and decreases colon cancer cell stemness.Therefore,by reducing the recommended amount of 5-FU,this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.展开更多
When oleanolic acid (OA) was administered ig before and after sensitization on d 1 to d 5 and d 11 to d 17,it had no apparent effect on Arthus reaction.When it was administered at 48,24 and 1 h before challenge,howeve...When oleanolic acid (OA) was administered ig before and after sensitization on d 1 to d 5 and d 11 to d 17,it had no apparent effect on Arthus reaction.When it was administered at 48,24 and 1 h before challenge,however,Arthus reaction was significantly inhibited.OA showed markedly suppressive effects on reversible passive Arthus reaction and leukocyte migratory response.It could significantly stabilize erythrocyte membrane,inhibit the swelling of the rat's hind paw induced by in- jecting mycostatin,reduce the acid phosphatase content in the inflammatory exudate,suppress the syn- thesis or release of PGE,histamine,LTB4 and kinin,and the phlogistic action of PGE_2,histamine,5- HT and kinin.In addition,it could decrease the content of malonyldialdehyde (MDA) in hepatic tissue of alcohol-intoxicated mice,and increase the activity of catalase (CAT) in hepatic tissue of mice.OA had no apparent effect on the activity of super-oxide dismutase (SOD) in rat serum,on the content of immune complex in serum of rat with Arthus reaction,on the phagocytosis of monocytc-macrophage system,on the clearance of enzyme-containing immune complex by macrophage,or on the activity of total complement.展开更多
The compound 15α-hydroxyl-oleanolic acid was biotransformed from oleanolic acid with Colletotrichum lini AS3.4486,and its structure was characterized by 1H NMR,13C NMR,HR-ESI-MS and single-crystal X-ray diffraction.T...The compound 15α-hydroxyl-oleanolic acid was biotransformed from oleanolic acid with Colletotrichum lini AS3.4486,and its structure was characterized by 1H NMR,13C NMR,HR-ESI-MS and single-crystal X-ray diffraction.The crystal of the title compound belongs to monoclinic,space group R3 with a=34.255（5）,b=34.255（5）,c=6.8671（14）,β=90°,Z=9,V=6978（2）3,Mr=490.70,Dc=1.051 mg/m3,μ=0.069 mm-1,F（000）=2430,R=0.0375 and wR=0.0808.The title compound is stacked into a three-dimensional network through hydrogen bonds.展开更多
Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were...Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were（104.5±11.7）nm, （-25.5±1.8）mV,（94.2±3.9）%,and（4.71±0.15）%,respectively.The morphology was illustrated by TEM as sphere stuffed particles.The XRD and DSC spectra confirmed that the OA molecules were dispersed uniformly into SLN matrixes.The results of in vitro release test suggested that OA was released slowly at a rate of 4.88%per hour from SLN preparation,which was consistent with the Zero-order Released Model.In addition,OA-SLNs were stable in artificial gastric juice and artificial intestinal juice.Together,our results provided new data for the potential application of OA-SLNs in oral administration.展开更多
AIM: Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a similar chemical structure and are distributed wildly in plants all over the world. In recent years, it was found that they had marked anti-...AIM: Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a similar chemical structure and are distributed wildly in plants all over the world. In recent years, it was found that they had marked anti-tumor effects. There is little literature currently available regarding their effects on colon carcinoma cells. The present study was designed to investigate their inhibitory effects on human colon carcinoma cell line HCT15. METHODS: HCT15 cells were cultured with different drugs. The treated cells were stained with hematoxylin-eosin and their morphologic changes observed under a light microscope. The cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means +/-SEM and Analysis of variance and Student' t-test for individual comparisons. RESULTS: Twenty-four to 72 h after UA or OA 60 micromol/L treatment, the numbers of dead cells and cell fragments were increased and most cells were dead at the 72nd hour. The cytotoxicity of UA was stronger than that of OA. Seventy-eight hours after 30 micromol/L of UA or OA treatment, a number of cells were degenerated, but cell fragments were rarely seen. The IC(50) values for UA and OA were 30 and 60 micromol/L, respectively. Proliferation assay showed that proliferation of UA and OA-treated cells was slightly increased at 24h and significantly decreased at 48 h and 60 h, whereas untreated control cells maintained an exponential growth curve. Cell cycle analysis by FCM showed HCT15 cells treated with UA 30 and OA 60 for 36 h and 72 h gradually accumulated in G(0)/G(1) phase (both drugs P【0.05 for 72 h), with a concomitant decrease of cell populations in S phase (both drugs P【0.01 for 72 h) and no detectable apoptotic fraction. CONCLUSION: UA and OA have significant anti-tumor activity. The effect of UA is stronger than that of OA. The possible mechanism of action is that both drugs have an inhibitory effect on tumor cell proliferation through cell-cycle arrest.展开更多
BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. ...BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacriifced 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were mea-sured with quantitative real-time RT-PCR and Western blotting. RESULTS: The serum aminotransferases level and scores of he-patic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P<0.01). Compared with the IR group, OA pretreatment signiifcantly up-regulated the expression of Sesn2, PI3K, Akt and HO-1 in IR livers (P<0.05). Administration of zinc protoporphyrin (ZnPP), an inhibitor of HO-1, diminished the OA effect on HO-1 and Sesn2 expressions (P<0.05) and the protective effect of OA on IRI. CONCLUSIONS: Our results demonstrate that OA can attenu-ate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.展开更多
Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c ...Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.展开更多
Oleanolic acid(OA)and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerat...Oleanolic acid(OA)and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerative colitis,multiple sclerosis,metabolic disorders,diabetes,hepatitis and different cancers.This review assembles and presents the latest in vivo reports on the impacts of OA and OA derivatives from various plant sources and the biological mechanisms of OA activities.Thus,this review presents sufficient data proposing that OA and its derivatives are potential alternative and complementary therapies for the treatment and management of several diseases.展开更多
AIM: To investigate H<sub>2</sub>O<sub>2</sub>-induced promotion proliferation and malignant transformation in WB-F344 cells and anti-tumor effects of ursolic acid (UA) and oleanolic acid (OA).
Oleanolic acid(OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970 s. In our...Oleanolic acid(OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970 s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks(4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 m RNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 m RNAs were up-regulated and 4 m RNAs were down-regulated significantly after OA treatment. Five m RNAs(CACNA1 B, FCN, STEAP3, AMPH, and NR6 A1) were selected to validate the expression levels by q RT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.展开更多
The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA am...The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA.展开更多
The purpose of this study was to prepare the oleanolic acid–phospholipid complex (OAPC) and then solidify it employing fumed silica by simple solvent evaporation technique to improve dissolution rate of oleanolic aci...The purpose of this study was to prepare the oleanolic acid–phospholipid complex (OAPC) and then solidify it employing fumed silica by simple solvent evaporation technique to improve dissolution rate of oleanolic acid and oleanolic acid–phospholipid complex. The process of OA-PC was optimized and the type and proportion of fumed silica were studied by dissolution text. The structures of the phospholipid complex and solidified powder were also characterized by differential scanning calorimetry, X-ray diffraction, and scanning electron microscope. In the dissolution tests, OA from solidified powder was further released compared with that from pure OA and OA-PC in different kinds of dissolution media. These results suggest that the method of preparing solidified powder of oleanolic acid–phospholipid complex is suitable for enhancing the dissolution rate of OA and OA-PC.展开更多
Considering that high levels of nitric oxide(NO) exert anti-cancer effect and the derivatives of oleanolic acid(OA) have shown potent anti-cancer activity, new O^2-vinyl diazeniumdiolate-based NO releasing derivatives...Considering that high levels of nitric oxide(NO) exert anti-cancer effect and the derivatives of oleanolic acid(OA) have shown potent anti-cancer activity, new O^2-vinyl diazeniumdiolate-based NO releasing derivatives(5a–l, 11a–l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and Hep G2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.展开更多
OBJECTIVE： Oleanolic acid （OA） has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular ...OBJECTIVE： Oleanolic acid （OA） has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation. METHODS： Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor （EGFR） activity were performed. To investigate whether cells undergo apoptosis, studies like fluorescence microscopy, poly （ADP-ribose） polymerase （PARP） degradation, annexin V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed. RESULTS： OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells （skin keratinocytes） and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an anti- proliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondria- dependent caspase 3-mediated apoptosis. CONCLUSION： OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent.展开更多
Stroke is considered the most common and severely disabling neurological disease. It is one of the leading causes of death after heart disease and cancer, causing 10% deaths worldwide and involving risk factors such a...Stroke is considered the most common and severely disabling neurological disease. It is one of the leading causes of death after heart disease and cancer, causing 10% deaths worldwide and involving risk factors such as smoking, obesity and nutritional disbalance. Disability affects 75% of stroke survivors through severe mental and/or physical impairment depending on the affected brain area （Go et al., 2014）.展开更多
Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases,such as cancer,rheumatoid arthritis,and age-related macular degeneration.Recent studies have r...Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases,such as cancer,rheumatoid arthritis,and age-related macular degeneration.Recent studies have revealed that oleanolic acid(OA),a natural pentacyclic triterpenoid,inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs,which may represent an attractive VEGF inhibitor.In this paper,rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential.As a result,a series of novel OA derivatives,possessingα,β-unsat-urated ketone system in ring A and amide functional group at C-28,were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs.The results showed that two promising derivatives,OA-1 and OA-16,exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs,compared with OA.The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VE-GFR2 activation.Furthermore,small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2.Thus,the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors,which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.展开更多
Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solu...Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects.To solve the problems,we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug,poly[oligo(ethylene glycol)methyl ether methacrylate]-b-poly(oleanolic acid methacrylate)(POEGMA-b-POAMA),encapsulating 10-hydroxycamptothecin(HCPT)to achieve efficient cancer therapy.The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization(RAFT),and could selfassemble to prepare POEGMA-b-POAMA/HCPT nanoparticles(NPs).The obtained nanoparticles exhibited appropriate particle size,excellent drug stability,good drug loading capacity,and high drug loading efficiency.In vitro drug release indicated that the drug release was prolonged to 132 h.The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells.Furthermore,in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor.Therefore,POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant No.31972580 and U21A20252)the China Agriculture Research System(CARS-35)+1 种基金the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2022C002)the Support Project of Young Leading Talents of Northeast Agricultural University(NEAU2023QNLJ-017)。
文摘Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work demonstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P<0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P<0.05).This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-PKA-CREB signaling pathway(P<0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P<0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.
基金supported by the Lianyungang Postdoctoral Research Funding Program(No.LYG20210018).
文摘Oleanolic acid(OA),a pentacyclic triterpenoid,exhibits a broad spectrum of biological activities,including antitumor,antiviral,antibacterial,anti-inflammatory,hepatoprotective,hypoglycemic,and hypolipidemic effects.Since its initial isolation and identification,numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives.Despite this,there has been a dearth of comprehensive reviews in the past two decades,leading to challenges in subsequent research on OA.Based on the main biological activities of OA,this paper comprehensively summarized the modification strategies and structureactivity relationships(SARs)of OA and its derivatives to provide valuable reference for future investigations into OA.
基金supported by the National Natural Science Foundation of China(82060598,32260587)the Scientific Research Program of Guizhou Provincial Department of Education(QJJ[2023]019)+1 种基金the Science&Technology Program of Guizhou Province(QKHPTRC-CXTD[2022]014)the Excellent Youth Talents of Zunyi Medical University(17zy-006).
文摘Oleanolic acid(OA)and ursolic acid(UA)are commonly present in the cuticular wax of many edible fruits and medicinal herbs.OA and UA belong to the group of bioactive pentacyclic triterpenoids,exhibiting a wide range of beneficial effects including protection for the kidneys,liver,heart,gastrointestinal tract,and spinal cord.Additionally,OA and UA exhibit antioxidant,anti-ferroptotic,anti-apoptotic,anti-inflammatory,anti-tumor,anti-viral,anti-diabetic,anti-microbial,anti-parasitic,analgesic,wound-healing,hypolipidemic,and hypoglycemic properties,often without notable side effects.Due to the extensive array of their positive functions,it is not feasible to thoroughly cover all aspects in this review.Therefore,the primary focus lies on reviewing the natural sources,extraction,and nephroprotective properties of OA and UA.To summarize,current literatures highlight the nephroprotective mechanisms of OA and UA,primarily involving inhibiting oxidative stress,endoplasmic reticulum stress,glycative stress,dyslipidemia,inflammation,apoptosis,pyroptosis,and renal fibrosis,promoting diuresis,as well as fine-tuning autophagy.
基金The work was supported by grants from the Scientific Research Projects of Medical and Health Institutions of Longhua District,Shenzhen(2021016)Shenzhen Basic Research Project(JCYJ20210324125803008).
文摘Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal herbs.Conversely,the OA that impacts colon cancer(CC)cells and its underlying mechanisms remain poorly understood.Methods:The cytotoxic effect of OA alone or OA-5-Fluorouracil(5-FU)combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide(MTT).Then,the impact of OA on CC cell lines(LoVo and HT-29)proliferation and stemness were measured using colon formation and tumorsphere formation assays.Octamer-binding transcription factor 4(Oct4),Prominin-1(CD133),Nanog,and transcription factor SOX-2(SOX2)are cell stemness-related indicators whose expression was assessed usingfluorescence qPCR assay,Western blotting,and immunohistochemistry.The effect of OA on the proliferative potency of CC cells was evaluated using an in vivo model.Results:The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU.Moreover,OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers(CD133,Nanog,SOX2,and Oct4)expression levels both in vitro and in vivo,as well as by inactivating the activator of transcription 3(STAT3 signaling)and Janus kinase 2/signal transducer(JAK2).Conclusion:Thesefindings imply that oleanolic acid,both in vitro and in vivo,suppresses the JAK2/STAT3 pathway,which in turn reverses chemoresistance and decreases colon cancer cell stemness.Therefore,by reducing the recommended amount of 5-FU,this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.
文摘When oleanolic acid (OA) was administered ig before and after sensitization on d 1 to d 5 and d 11 to d 17,it had no apparent effect on Arthus reaction.When it was administered at 48,24 and 1 h before challenge,however,Arthus reaction was significantly inhibited.OA showed markedly suppressive effects on reversible passive Arthus reaction and leukocyte migratory response.It could significantly stabilize erythrocyte membrane,inhibit the swelling of the rat's hind paw induced by in- jecting mycostatin,reduce the acid phosphatase content in the inflammatory exudate,suppress the syn- thesis or release of PGE,histamine,LTB4 and kinin,and the phlogistic action of PGE_2,histamine,5- HT and kinin.In addition,it could decrease the content of malonyldialdehyde (MDA) in hepatic tissue of alcohol-intoxicated mice,and increase the activity of catalase (CAT) in hepatic tissue of mice.OA had no apparent effect on the activity of super-oxide dismutase (SOD) in rat serum,on the content of immune complex in serum of rat with Arthus reaction,on the phagocytosis of monocytc-macrophage system,on the clearance of enzyme-containing immune complex by macrophage,or on the activity of total complement.
基金supported by the starting Foundation of Tianjin University of Science and Technology (No. 20070449)the Natural Science Foundation of Tianjin (Nos. 08JCZDJC15200 and 08JCZDJC15300)
文摘The compound 15α-hydroxyl-oleanolic acid was biotransformed from oleanolic acid with Colletotrichum lini AS3.4486,and its structure was characterized by 1H NMR,13C NMR,HR-ESI-MS and single-crystal X-ray diffraction.The crystal of the title compound belongs to monoclinic,space group R3 with a=34.255（5）,b=34.255（5）,c=6.8671（14）,β=90°,Z=9,V=6978（2）3,Mr=490.70,Dc=1.051 mg/m3,μ=0.069 mm-1,F（000）=2430,R=0.0375 and wR=0.0808.The title compound is stacked into a three-dimensional network through hydrogen bonds.
基金National Basic Research Program of China(973 Program Grant No.2009CB930300)National Integrity Innovational Technology Platform of New Drug and Research and Development (Grant No.2009ZX09310-001).
文摘Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were（104.5±11.7）nm, （-25.5±1.8）mV,（94.2±3.9）%,and（4.71±0.15）%,respectively.The morphology was illustrated by TEM as sphere stuffed particles.The XRD and DSC spectra confirmed that the OA molecules were dispersed uniformly into SLN matrixes.The results of in vitro release test suggested that OA was released slowly at a rate of 4.88%per hour from SLN preparation,which was consistent with the Zero-order Released Model.In addition,OA-SLNs were stable in artificial gastric juice and artificial intestinal juice.Together,our results provided new data for the potential application of OA-SLNs in oral administration.
文摘AIM: Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a similar chemical structure and are distributed wildly in plants all over the world. In recent years, it was found that they had marked anti-tumor effects. There is little literature currently available regarding their effects on colon carcinoma cells. The present study was designed to investigate their inhibitory effects on human colon carcinoma cell line HCT15. METHODS: HCT15 cells were cultured with different drugs. The treated cells were stained with hematoxylin-eosin and their morphologic changes observed under a light microscope. The cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means +/-SEM and Analysis of variance and Student' t-test for individual comparisons. RESULTS: Twenty-four to 72 h after UA or OA 60 micromol/L treatment, the numbers of dead cells and cell fragments were increased and most cells were dead at the 72nd hour. The cytotoxicity of UA was stronger than that of OA. Seventy-eight hours after 30 micromol/L of UA or OA treatment, a number of cells were degenerated, but cell fragments were rarely seen. The IC(50) values for UA and OA were 30 and 60 micromol/L, respectively. Proliferation assay showed that proliferation of UA and OA-treated cells was slightly increased at 24h and significantly decreased at 48 h and 60 h, whereas untreated control cells maintained an exponential growth curve. Cell cycle analysis by FCM showed HCT15 cells treated with UA 30 and OA 60 for 36 h and 72 h gradually accumulated in G(0)/G(1) phase (both drugs P【0.05 for 72 h), with a concomitant decrease of cell populations in S phase (both drugs P【0.01 for 72 h) and no detectable apoptotic fraction. CONCLUSION: UA and OA have significant anti-tumor activity. The effect of UA is stronger than that of OA. The possible mechanism of action is that both drugs have an inhibitory effect on tumor cell proliferation through cell-cycle arrest.
基金supported by grants from the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,Basic Research Program-Youth Fund Project of Jiangsu Province(BK20140092)the National Natural Science Foundation of China(81400650,81470901,81273261 and 81270583)
文摘BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacriifced 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were mea-sured with quantitative real-time RT-PCR and Western blotting. RESULTS: The serum aminotransferases level and scores of he-patic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P<0.01). Compared with the IR group, OA pretreatment signiifcantly up-regulated the expression of Sesn2, PI3K, Akt and HO-1 in IR livers (P<0.05). Administration of zinc protoporphyrin (ZnPP), an inhibitor of HO-1, diminished the OA effect on HO-1 and Sesn2 expressions (P<0.05) and the protective effect of OA on IRI. CONCLUSIONS: Our results demonstrate that OA can attenu-ate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.
基金partly supported by Grant from the Instituto Mexicano del Seguro Social (NO.FIS/IMSS/PROT/G12/1126FIS/IMSS/PROT/G14/1341)
文摘Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.
文摘Oleanolic acid(OA)and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerative colitis,multiple sclerosis,metabolic disorders,diabetes,hepatitis and different cancers.This review assembles and presents the latest in vivo reports on the impacts of OA and OA derivatives from various plant sources and the biological mechanisms of OA activities.Thus,this review presents sufficient data proposing that OA and its derivatives are potential alternative and complementary therapies for the treatment and management of several diseases.
基金Supported by The Natural Science Foundation of Beijing Municipality,China,No.7112010the National Natural Science Foundation of China,No.81272757the Education Commission Research Program of Beijing Municipality,China,No.KM201010025004
文摘AIM: To investigate H<sub>2</sub>O<sub>2</sub>-induced promotion proliferation and malignant transformation in WB-F344 cells and anti-tumor effects of ursolic acid (UA) and oleanolic acid (OA).
基金supported by National Natural Science Foundation of China(Nos.81673443,81373303 and 31501182)by the Fundamental Research Funds for the Central Universities(No.26302017ZD05)
文摘Oleanolic acid(OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970 s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks(4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 m RNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 m RNAs were up-regulated and 4 m RNAs were down-regulated significantly after OA treatment. Five m RNAs(CACNA1 B, FCN, STEAP3, AMPH, and NR6 A1) were selected to validate the expression levels by q RT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.
基金financially supported by National Natural Science Foundation of China (No. 81502993)Doctoral Research Funding of Liaoning Province (No. 20141066)+1 种基金General Project in Department of Education of Liaoning Province (No. L2014379)Career Development Program for Young Teachers in Shenyang Pharmaceutical University
文摘The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA.
文摘The purpose of this study was to prepare the oleanolic acid–phospholipid complex (OAPC) and then solidify it employing fumed silica by simple solvent evaporation technique to improve dissolution rate of oleanolic acid and oleanolic acid–phospholipid complex. The process of OA-PC was optimized and the type and proportion of fumed silica were studied by dissolution text. The structures of the phospholipid complex and solidified powder were also characterized by differential scanning calorimetry, X-ray diffraction, and scanning electron microscope. In the dissolution tests, OA from solidified powder was further released compared with that from pure OA and OA-PC in different kinds of dissolution media. These results suggest that the method of preparing solidified powder of oleanolic acid–phospholipid complex is suitable for enhancing the dissolution rate of OA and OA-PC.
基金supported by grants from the National Natural Science Foundation of China(Nos.81273378 and 21372261)
文摘Considering that high levels of nitric oxide(NO) exert anti-cancer effect and the derivatives of oleanolic acid(OA) have shown potent anti-cancer activity, new O^2-vinyl diazeniumdiolate-based NO releasing derivatives(5a–l, 11a–l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and Hep G2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.
基金the Boiron Laboratories,Lyon,France for partial financial support of the work
文摘OBJECTIVE： Oleanolic acid （OA） has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation. METHODS： Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor （EGFR） activity were performed. To investigate whether cells undergo apoptosis, studies like fluorescence microscopy, poly （ADP-ribose） polymerase （PARP） degradation, annexin V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed. RESULTS： OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells （skin keratinocytes） and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an anti- proliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondria- dependent caspase 3-mediated apoptosis. CONCLUSION： OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent.
基金supported by UBACYT 20020130100258BA(A.B.)PIP CONICET 00269(A.B.)UBACYT 20020130300033BA(L.C.)
文摘Stroke is considered the most common and severely disabling neurological disease. It is one of the leading causes of death after heart disease and cancer, causing 10% deaths worldwide and involving risk factors such as smoking, obesity and nutritional disbalance. Disability affects 75% of stroke survivors through severe mental and/or physical impairment depending on the affected brain area （Go et al., 2014）.
基金supported by the National Natural Science Foundation of China(Nos.21672082 and 31671214)the Natural Science Foundation of Shandong Province(Nos.ZR2019YQ31,ZR2020YQ52,and ZR2020MB103)+1 种基金the Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program(No.2020KJE006)the Science and Technology Project of University of Jinan(No.XKY2004).
文摘Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases,such as cancer,rheumatoid arthritis,and age-related macular degeneration.Recent studies have revealed that oleanolic acid(OA),a natural pentacyclic triterpenoid,inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs,which may represent an attractive VEGF inhibitor.In this paper,rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential.As a result,a series of novel OA derivatives,possessingα,β-unsat-urated ketone system in ring A and amide functional group at C-28,were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs.The results showed that two promising derivatives,OA-1 and OA-16,exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs,compared with OA.The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VE-GFR2 activation.Furthermore,small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2.Thus,the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors,which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.
基金This work was financially supported by the National Natural Science Foundation of China(No.21576029)National Key R&D Program of China(No.2017YFD0601205).
文摘Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects.To solve the problems,we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug,poly[oligo(ethylene glycol)methyl ether methacrylate]-b-poly(oleanolic acid methacrylate)(POEGMA-b-POAMA),encapsulating 10-hydroxycamptothecin(HCPT)to achieve efficient cancer therapy.The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization(RAFT),and could selfassemble to prepare POEGMA-b-POAMA/HCPT nanoparticles(NPs).The obtained nanoparticles exhibited appropriate particle size,excellent drug stability,good drug loading capacity,and high drug loading efficiency.In vitro drug release indicated that the drug release was prolonged to 132 h.The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells.Furthermore,in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor.Therefore,POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.
