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:Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells.Our study is the first to demonstrate the strong inhibitory effects of ursolic...Background:Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells.Our study is the first to demonstrate the strong inhibitory effects of ursolic acid on the proliferation of cutaneous T-cell lymphoma(CTCL)cells.We aimed to further investigate the underlying mechanism of the proliferation inhibition induced by ursolic acid in CTCL cells using transcriptome sequencing.Methods:Cell counting kit-8 assays were used to observe the effects of six traditional medicine monomers on the proliferation of CTCL cells.Transcriptome sequencing was used to identify differentially expressed genes after ursolic acid treatment.Bioinformatics analysis was performed to determine the potential mechanism.Real-time quantitative PCR and western blotting analyses were performed to confirm the sequencing results and verify the possible mechanisms of ursolic acid-mediated proliferation inhibition in CTCL cells.Results:Ursolic acid exhibited the strongest inhibitory effect on the proliferation of CTCL cells among the six traditional medicine monomers.Transcriptome sequencing analysis showed that 2,466 genes were significantly altered.Combined with Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction network analysis,the interaction of various pathways and signaling molecules,such as tumor necrosis factor-α,NLR family pyrin domain containing 1,c-Jun N-terminal kinase,and melanoma differentiation-associated gene 5,accounted for the anti-tumor effects of ursolic acid in CTCL cells.Conclusion:Ursolic acid significantly inhibited the proliferation of CTCL cells,and our study laid a theoretical foundation for the future treatment of CTCL using ursolic acid.展开更多
This study examined the effects of ursolic acid (UA) on the proliferation and apoptosis of a human ovarian cancer cell line, CAOV3. The CAOV3 cells were cultured in the RPMI 1640 media and treated with different con...This study examined the effects of ursolic acid (UA) on the proliferation and apoptosis of a human ovarian cancer cell line, CAOV3. The CAOV3 cells were cultured in the RPMI 1640 media and treated with different concentrations of UA (0, 10, 20, 40 μmol/L). The proliferation rate of the CAOV3 cells was determined by MTT assay. The apoptosis rate was measured by flow cytometry. ERK activity was detected by immunoprecipitation and the expressions of p-ERK1/2, MKP-1, Bax and Bcl-2 by Western blotting. The results showed that the proliferation rate was significantly decreased in the cells treated with UA as compared with that in the non-treated cells (P〈0.05). The intracellular ERK activity and p-ERK1/2 expression were also reduced in the UA-treated cells, while the MKP-1 expression was elevated. Moreover, the apoptosis was found in the CAOV3 cells exposed to UA; the Bax expression was increased and the Bcl-2 expression decreased. The apoptosis rate in the UA-treated cells was much higher than that in the non-treated cells (P〈0.05). It is concluded that UA can inhibit the proliferation of CAOV3 cells by suppressing the ERK activity and the expression of p-ERK1/2. And it can also induce the apoptosis of the CAOV3 cells by up-regulating the Bax expression and down-regulating the Bcl-2 expression.展开更多
Ursolic acid was modified at C3 and C28 position to obtain fourteen derivatives including twelve novel compounds, and their chemical structures were characterized by IR, ^1H NMR and MS. Cell growth inhibitory effects ...Ursolic acid was modified at C3 and C28 position to obtain fourteen derivatives including twelve novel compounds, and their chemical structures were characterized by IR, ^1H NMR and MS. Cell growth inhibitory effects of the derivatives against Hela cell were evaluated by MTT assay. All these derivatives were found to have stronger cell growth inhibitory than their parent compound, ursolic acid. The derivatives with a substituted acetyl group at C3 hydroxyl group show better activities than those with an unsubstituted hydroxyl group.展开更多
Objective: To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo. Methods: Atransplanted tumor model by injecting Eca-109 cells into subcutaneous tissue o...Objective: To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo. Methods: Atransplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established. 40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid (25-100 mg·kg^-1·d^-1) was injected into abdominal cavity respectively once everyday and lasted for fourteen days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. The morphological changes of apoptosis were observed by electron microscope. The expressions of COX-2, bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry. At last the PGE2 level of transplanted tumors was detected byradioimmunoassay. Results: Treatment of nude mice with 25, 50, or 100 mg·kg^-1·d^-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses. The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups, while the Bax increased. The PGE2 level of transplanted tumors was decreased in ursolic acid groups with adose-relatedmanner. Conclusion: Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo, which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.展开更多
Objective: To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil (5-FU) on human esophageal carcinoma cell Eca-109 in vitro. Methods: Eca-109 cells were treated with ur...Objective: To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil (5-FU) on human esophageal carcinoma cell Eca-109 in vitro. Methods: Eca-109 cells were treated with ursolic acid (10-50 μmol/L) and/or 5-fluorouracil (48.0-768.8 μmol/L) for 48 h in vitro. And then cell proliferation was determined by MTT assay. Cell cycle and apoptosis rate were analyzed by flow cytometry (FCM). The morphological changes of apoptosis were observed by fluorescent microscopy. At last the expression of P27kipl, bcl-2 and bax were detected by western blot. Results: Results: In comparison with single agent treatment, the combination of ursolic acid and 5-fluorouracil produced greater efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction (P〈0.05). Western blot analysis showed that the combination use of ursolic acid and 5-fluorouracil suppressed the expression of bcl-2 and increased the expressions of bax and P27kip1. Conclusion: Ursolic acid combined with 5-fluorouracil showed adjuvant antiproliferative effects on human esophageal carcinoma cell Eca-109 in vitro, which mainly due to the induction of cell cycle arrest as well as apoptosis.展开更多
Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its f...Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its further clinical application.Recently,with the development of nanotechnology,various UA nanosystems have emerged as promising strategies for effective cancer therapy.This article reviews various types of UA-based nanodelivery systems,primarily with emphasis placed on novel UA-based carrier-free nanodrugs,which are considered to be innovative methods for cancer therapy.Moreover,this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance.Finally,the article also describes the development and challenges of UA nanosystems for future research in this field.Overall,the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.展开更多
Oleanolic acid(OA) and ursolic acid(UA) are isomeric triterpenic acids and only one methyl’s position is different between them.OA and UA always exist in the same plant,so it is difficult to separate them when determ...Oleanolic acid(OA) and ursolic acid(UA) are isomeric triterpenic acids and only one methyl’s position is different between them.OA and UA always exist in the same plant,so it is difficult to separate them when determining contents by RP-HPLC.In this study,a very simple mobile phase for HPLC was developed to simultaneously determine UA and OA,and the factors affecting separation were also discussed.The mobile phase is methanol:water(95:5) with flow rate 0.4 mL/min.The retention time for OA and UA was 20.58 and 21.57 min,respectively,the resolution was 1.61.The average contents of OA and UA of three Loquat leaves sets were 1.4 mg/g and 5.6 mg/g,respectively.Regarding the HPLC,we found that changing mobile phase,adjusting the pH value or adding ion-pairing agent could not affect the separation between UA and OA greatly.While adjustment of the flow rate and column temperature could improve the resolution greatly.展开更多
In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve c...In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuber-osity. The successful y generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradual y increased at 1-4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L 4-6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice fol owing sciatic nerve injury.展开更多
Ursolic acid(UA) and oleanolic acid(OA) are insoluble drugs. The objective of this study was to encapsulate them into β-cyclodextrin(β-CD) and compare the solubility and intermolecular force of β-CD with the two is...Ursolic acid(UA) and oleanolic acid(OA) are insoluble drugs. The objective of this study was to encapsulate them into β-cyclodextrin(β-CD) and compare the solubility and intermolecular force of β-CD with the two isomeric triterpenic acids. The host-guest interaction was explored in liquid and solid state by ultraviolet-visible absorption,1H NMR, phase solubility analysis, and differential scanning calorimetry, X-ray powder diffractometry, and molecular modeling studies. Both experimental and theoretical studies revealed that β-CD formed 1: 1 water soluble inclusion complexes and the complexation process was naturally favorable. In addition, the overall results suggested that ring E with a carboxyl group of the drug was encapsulated into the hydrophobic CD nanocavity. Therefore, a clear different inclusion behavior was observed, and UA exhibited better affinity to β-CD compared with OA in various media due to little steric interference, which was beneficial to form stable inclusion complex with β-CD and increase its water solubility effectively.展开更多
OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo,and to explore the underlying mechanism.METHODS The smoothened(SMO)gene-silenced human colorectal ...OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo,and to explore the underlying mechanism.METHODS The smoothened(SMO)gene-silenced human colorectal cancer HCT116^(hSMO)cell line was established by transfection with the lentivirus carrying SMO shRNA.The cytotoxic effect of ursolic acid on HCT116^(hSMO)cells was determined by MTT assay.The effect of ursolic acid on the migration of HCT116^(hSMO)cells was studied by wound healing assay.The effect of ursolic acid on apoptosis of HCT116^(hSMO)cells was explored by Hoechst33342/PI double staining and flow cytometry.The effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2,Bax,caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR(RT-qPCR)and Western blotting(WB)analysis.RT-qPCR and WB were used to examine the relationship between GLI1,c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116^(hSMO)cells.The effects of ursolic acid on the expressions of GLI1,p-Akt,Akt,c-Myc,SHH and SUFU of noncanonical Hedgehog pathway were evaluated by RT-qPCR and WB assays.Xenograft nude mouse model bearing HCT116^(hSMO)cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in vivo.The body weight and tumor size of mice were assessed regularly every 2 d.The effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL assay.The expressions of Bcl-2,Bax,GLI1,p-Akt,Akt,c-Myc,SHH,SUFU mRNA and proteins were measured by RT-qPCR and WB.The levels of Bcl-2,Bax,GLI1,p-Akt,c-Myc and SHH proteins in tumor tissues were also evaluated by immunohistochemistry.RESULTS Ursolic acid significantly inhibited the growth and migration of HCT116^(hSMO)cells in vitro,compared with the control(P<0.05).Meanwhile,ursolic acid also induced apoptosis of HCT116^(hSMO)cells in vitro(P<0.05).Furthermore,SC79(Akt activator)enhanced the expressions of p-Akt,GLI1 and c-Myc,which could be abolished by ursolic acid,and the effect was equal to Akt inhibitor LY294002.The expressions of Bcl-2,GLI1,p-Akt,c-Myc,SHH mRNA and proteins were reduced by ursolic acid,while the levels of Bax and SUFU were increased.Ursolic acid could inhibit the growth and induce the apoptosis of colorectal cancer xenograft in vivo.Similarly,lower levels of Bcl-2,GLI1,p-Akt,c-Myc and SHH,and higher expression of Bax and SUFU were noted in ursolic acid-treated mice.CONCLUSION Ursolic acid can inhibit the growth and induce apoptosis of HCT116^(hSMO)cells both in vitro and in vivo.And the mechanism is related to the suppression of PI3K/Akt-mediated noncanonical Hedgehog signaling pathway.展开更多
OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was esta...OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.展开更多
The title compound(C(37)H(48)BrNO5, 6) was synthesized from ursolic acid and its crystal structure was determined by single-crystal X-ray diffraction analysis. The compound is of orthorhombic system, space group...The title compound(C(37)H(48)BrNO5, 6) was synthesized from ursolic acid and its crystal structure was determined by single-crystal X-ray diffraction analysis. The compound is of orthorhombic system, space group P212121 with a = 16.846(3), b = 18.844(4), c = 11.262(2)A, Z =4, V = 3575.1(13) A^3, Mr = 666.67, Dc = 1.239 Mg/m^3, S = 1.002, μ = 1.190 mm^-1, F(000) = 1408,the final R = 0.0831 and wR = 0.1459 for 2286 observed reflections(I 〉 2σ(I)). The crystal structure is stabilized by two intermolecular hydrogen bonds(N–H(0A)···O(2) and O(1)–H(1A)···O(3)). In the preliminary antitumor assay, the title compound 6 exhibits potent cytotoxic activity against Hep G2 and SMMC-7721 cells with IC50 values of 1.64 ± 0.21 and 1.22 ± 0.13 μM, respectively.展开更多
Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many ...Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.展开更多
The present study reports in vitro anti-sickling activity and phytochemical analyses of the leaves of Ocimum gratissimum.Biological testing revealed that the plant extracts possess antisickling effects.The combination...The present study reports in vitro anti-sickling activity and phytochemical analyses of the leaves of Ocimum gratissimum.Biological testing revealed that the plant extracts possess antisickling effects.The combination of spectroscopic techniques:1D-NMR,2D-NMR and MS revealed that ursolic acid is the major biologically active compound of O.gratissimum(Silva et al.in Molecules 13:2482–2487,2008;Kedar et al.J Food Drug Anal 20:865–871,2012).This study is the first report of the antisickling activity of ursolic acid isolated from O.gratissimum.The pharmaceutical relevance of findings from this study derives from the possibility of integrating O.gratissimum as an antisickling plant in the pharmacopoeia of Democratic Republic of the Congo.The identification of the active principle could enhance the standardization of antisickling recipe.展开更多
[Objectives]This study was conducted to establish a method for determining the contents of Chaenomeles cathayensis(Hemsl.)Schneid.,and analyze the changes in effective components of C.cathayensis grown in Guizhou,so a...[Objectives]This study was conducted to establish a method for determining the contents of Chaenomeles cathayensis(Hemsl.)Schneid.,and analyze the changes in effective components of C.cathayensis grown in Guizhou,so as to provide data support for the production and quality control of C.cathayensis.[Methods]The contents of ursolic acid and oleanolic acid in C.cathayensis in different areas of Guizhou were determined.The HPLC method was adopted under following conditions:chromatographic column waters C18 column(4.6 mm×150 mm,5.0μm);mobile phase:methanol-0.1 mol/L ammonium acetate(85∶15);column temperature:25℃;detection wavelength:257 nm;flow rate 1.0 ml/min.[Results]Through methodological investigations,HPLC could be used to detect the contents of the two terpenoids oleanolic acid and ursolic acid in C.cathayensis from Guizhou.The content of oleanolic acid ranged from 0.076%to 0.144%,and the content of ursolic acid ranged from 0.201%to 0.439%.[Conclusions]A method for determining the contents of C.cathayensis was established using the HPLC method with oleanolic acid and ursolic acid as the index components.The method is accurate,reliable,and simple and easy to implement,and can serve as a reference and support for quality evaluation and standard improvement of C.cathayensis.展开更多
<span style="font-family:Verdana;">In the present study, two cell-based systems for assessing Yang and Yin activities were for the first time used to investigate the effect of ursolic acid (UA) and ole...<span style="font-family:Verdana;">In the present study, two cell-based systems for assessing Yang and Yin activities were for the first time used to investigate the effect of ursolic acid (UA) and oleanolic acid (OA). The results indicated that while UA was only active in the Yang assay, OA produced activity in the Yin assay. The Yang/Yin activity of UA/OA may be attributed to their distinct molecular structures, which confer their differential ability to interact with mitochondrial membrane or cellular membrane lipids, with resultant membrane fluidization and potentiation of biological responses.</span>展开更多
Lung cancer is the major cause of death in the neoplastic diseases. In spite of the advances in the chemotherapy, the lung cancer treatments are still complex and costly, being necessary the seeking of new drugs. In t...Lung cancer is the major cause of death in the neoplastic diseases. In spite of the advances in the chemotherapy, the lung cancer treatments are still complex and costly, being necessary the seeking of new drugs. In this context, the ursolic acid (UA) becomes the target of studies that investigate its antitumor potential and, thus, structural modifications can enhance its biological activities. Eight UA semisynthetic derivative compounds (UAD1-8) were synthesized and evaluated their cytotoxic activity against human alveolar adenocarcinoma cells (A549). UAD1, UAD3, UAD5, UAD6 and UAD8 were able to reduce the viability of the A549 cells. Only UAD1 and UAD6 reduced the viability at 24 h, and only UAD3 didn’t reduce the NF-κB expression. The compound UAD1 showed the greater apoptosis induction. Moreover, the compound UAD1 showed better results than UA in all assays. The present study shows, for the first time, the action of these compounds in the apoptotic effect, in the expression of NF-κB and in the A549 cell line. The ursolic acid derivatives showed substantial results in the apoptosis, cytotoxicity and NF-κB inhibition of A549 cells, and further studies are necessary for the development of possible new therapeutic drugs.展开更多
Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological activities.To clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were desi...Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological activities.To clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)fluorophore.Among them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC_(50))=9.21±0.50μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent manner.Then,5c was found to localize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy studies.Preliminary MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and lysosome.In all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.展开更多
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This work was supported by the National Natural Science Foundation of China(No.82003808).
文摘Background:Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells.Our study is the first to demonstrate the strong inhibitory effects of ursolic acid on the proliferation of cutaneous T-cell lymphoma(CTCL)cells.We aimed to further investigate the underlying mechanism of the proliferation inhibition induced by ursolic acid in CTCL cells using transcriptome sequencing.Methods:Cell counting kit-8 assays were used to observe the effects of six traditional medicine monomers on the proliferation of CTCL cells.Transcriptome sequencing was used to identify differentially expressed genes after ursolic acid treatment.Bioinformatics analysis was performed to determine the potential mechanism.Real-time quantitative PCR and western blotting analyses were performed to confirm the sequencing results and verify the possible mechanisms of ursolic acid-mediated proliferation inhibition in CTCL cells.Results:Ursolic acid exhibited the strongest inhibitory effect on the proliferation of CTCL cells among the six traditional medicine monomers.Transcriptome sequencing analysis showed that 2,466 genes were significantly altered.Combined with Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction network analysis,the interaction of various pathways and signaling molecules,such as tumor necrosis factor-α,NLR family pyrin domain containing 1,c-Jun N-terminal kinase,and melanoma differentiation-associated gene 5,accounted for the anti-tumor effects of ursolic acid in CTCL cells.Conclusion:Ursolic acid significantly inhibited the proliferation of CTCL cells,and our study laid a theoretical foundation for the future treatment of CTCL using ursolic acid.
文摘This study examined the effects of ursolic acid (UA) on the proliferation and apoptosis of a human ovarian cancer cell line, CAOV3. The CAOV3 cells were cultured in the RPMI 1640 media and treated with different concentrations of UA (0, 10, 20, 40 μmol/L). The proliferation rate of the CAOV3 cells was determined by MTT assay. The apoptosis rate was measured by flow cytometry. ERK activity was detected by immunoprecipitation and the expressions of p-ERK1/2, MKP-1, Bax and Bcl-2 by Western blotting. The results showed that the proliferation rate was significantly decreased in the cells treated with UA as compared with that in the non-treated cells (P〈0.05). The intracellular ERK activity and p-ERK1/2 expression were also reduced in the UA-treated cells, while the MKP-1 expression was elevated. Moreover, the apoptosis was found in the CAOV3 cells exposed to UA; the Bax expression was increased and the Bcl-2 expression decreased. The apoptosis rate in the UA-treated cells was much higher than that in the non-treated cells (P〈0.05). It is concluded that UA can inhibit the proliferation of CAOV3 cells by suppressing the ERK activity and the expression of p-ERK1/2. And it can also induce the apoptosis of the CAOV3 cells by up-regulating the Bax expression and down-regulating the Bcl-2 expression.
基金Natural Science Foundation of Liaoning Province of China (No.20042009)Science and Technology Foundation of Shenyang City of China(No.20050785)
文摘Ursolic acid was modified at C3 and C28 position to obtain fourteen derivatives including twelve novel compounds, and their chemical structures were characterized by IR, ^1H NMR and MS. Cell growth inhibitory effects of the derivatives against Hela cell were evaluated by MTT assay. All these derivatives were found to have stronger cell growth inhibitory than their parent compound, ursolic acid. The derivatives with a substituted acetyl group at C3 hydroxyl group show better activities than those with an unsubstituted hydroxyl group.
基金the Natural Science Foundation Project of Chongqing Sci & Tech Committee (CSCT,2006BB5297).
文摘Objective: To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo. Methods: Atransplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established. 40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid (25-100 mg·kg^-1·d^-1) was injected into abdominal cavity respectively once everyday and lasted for fourteen days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. The morphological changes of apoptosis were observed by electron microscope. The expressions of COX-2, bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry. At last the PGE2 level of transplanted tumors was detected byradioimmunoassay. Results: Treatment of nude mice with 25, 50, or 100 mg·kg^-1·d^-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses. The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups, while the Bax increased. The PGE2 level of transplanted tumors was decreased in ursolic acid groups with adose-relatedmanner. Conclusion: Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo, which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.
基金supported by the grants from the Natural science Foundation Project of Chongqing Sci & Tech Committee (CSCT, 2006BB5297)
文摘Objective: To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil (5-FU) on human esophageal carcinoma cell Eca-109 in vitro. Methods: Eca-109 cells were treated with ursolic acid (10-50 μmol/L) and/or 5-fluorouracil (48.0-768.8 μmol/L) for 48 h in vitro. And then cell proliferation was determined by MTT assay. Cell cycle and apoptosis rate were analyzed by flow cytometry (FCM). The morphological changes of apoptosis were observed by fluorescent microscopy. At last the expression of P27kipl, bcl-2 and bax were detected by western blot. Results: Results: In comparison with single agent treatment, the combination of ursolic acid and 5-fluorouracil produced greater efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction (P〈0.05). Western blot analysis showed that the combination use of ursolic acid and 5-fluorouracil suppressed the expression of bcl-2 and increased the expressions of bax and P27kip1. Conclusion: Ursolic acid combined with 5-fluorouracil showed adjuvant antiproliferative effects on human esophageal carcinoma cell Eca-109 in vitro, which mainly due to the induction of cell cycle arrest as well as apoptosis.
基金supported by the National Natural Science Foundation of China(81972832,81472767)Scientific Research Training Program for Undergraduate of Fuzhou University(25055,25068)。
文摘Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its further clinical application.Recently,with the development of nanotechnology,various UA nanosystems have emerged as promising strategies for effective cancer therapy.This article reviews various types of UA-based nanodelivery systems,primarily with emphasis placed on novel UA-based carrier-free nanodrugs,which are considered to be innovative methods for cancer therapy.Moreover,this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance.Finally,the article also describes the development and challenges of UA nanosystems for future research in this field.Overall,the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.
文摘Oleanolic acid(OA) and ursolic acid(UA) are isomeric triterpenic acids and only one methyl’s position is different between them.OA and UA always exist in the same plant,so it is difficult to separate them when determining contents by RP-HPLC.In this study,a very simple mobile phase for HPLC was developed to simultaneously determine UA and OA,and the factors affecting separation were also discussed.The mobile phase is methanol:water(95:5) with flow rate 0.4 mL/min.The retention time for OA and UA was 20.58 and 21.57 min,respectively,the resolution was 1.61.The average contents of OA and UA of three Loquat leaves sets were 1.4 mg/g and 5.6 mg/g,respectively.Regarding the HPLC,we found that changing mobile phase,adjusting the pH value or adding ion-pairing agent could not affect the separation between UA and OA greatly.While adjustment of the flow rate and column temperature could improve the resolution greatly.
基金financially sponsored by the Science and Technology Ministry of Jilin Province,No.200705318
文摘In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuber-osity. The successful y generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradual y increased at 1-4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L 4-6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice fol owing sciatic nerve injury.
基金supported by grants from the National Natural Science Foundation of China (21303086)the Natural Science Foundation of Jiangsu Province (BK20130884)the Research Fund for Doctoral Program of Higher Education (20123234120012)
文摘Ursolic acid(UA) and oleanolic acid(OA) are insoluble drugs. The objective of this study was to encapsulate them into β-cyclodextrin(β-CD) and compare the solubility and intermolecular force of β-CD with the two isomeric triterpenic acids. The host-guest interaction was explored in liquid and solid state by ultraviolet-visible absorption,1H NMR, phase solubility analysis, and differential scanning calorimetry, X-ray powder diffractometry, and molecular modeling studies. Both experimental and theoretical studies revealed that β-CD formed 1: 1 water soluble inclusion complexes and the complexation process was naturally favorable. In addition, the overall results suggested that ring E with a carboxyl group of the drug was encapsulated into the hydrophobic CD nanocavity. Therefore, a clear different inclusion behavior was observed, and UA exhibited better affinity to β-CD compared with OA in various media due to little steric interference, which was beneficial to form stable inclusion complex with β-CD and increase its water solubility effectively.
基金National Natural Science Foundation of China(81573813,81173598)Sichuan Provincial Admin⁃istration of Traditional Chinese Medicine of China(2021MS447)+1 种基金Excellent Talent Program of Chengdu University of Tra⁃ditional Chinese Medicine of China(YXRC2019002,ZRYY1917)and Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006)。
文摘OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo,and to explore the underlying mechanism.METHODS The smoothened(SMO)gene-silenced human colorectal cancer HCT116^(hSMO)cell line was established by transfection with the lentivirus carrying SMO shRNA.The cytotoxic effect of ursolic acid on HCT116^(hSMO)cells was determined by MTT assay.The effect of ursolic acid on the migration of HCT116^(hSMO)cells was studied by wound healing assay.The effect of ursolic acid on apoptosis of HCT116^(hSMO)cells was explored by Hoechst33342/PI double staining and flow cytometry.The effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2,Bax,caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR(RT-qPCR)and Western blotting(WB)analysis.RT-qPCR and WB were used to examine the relationship between GLI1,c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116^(hSMO)cells.The effects of ursolic acid on the expressions of GLI1,p-Akt,Akt,c-Myc,SHH and SUFU of noncanonical Hedgehog pathway were evaluated by RT-qPCR and WB assays.Xenograft nude mouse model bearing HCT116^(hSMO)cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in vivo.The body weight and tumor size of mice were assessed regularly every 2 d.The effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL assay.The expressions of Bcl-2,Bax,GLI1,p-Akt,Akt,c-Myc,SHH,SUFU mRNA and proteins were measured by RT-qPCR and WB.The levels of Bcl-2,Bax,GLI1,p-Akt,c-Myc and SHH proteins in tumor tissues were also evaluated by immunohistochemistry.RESULTS Ursolic acid significantly inhibited the growth and migration of HCT116^(hSMO)cells in vitro,compared with the control(P<0.05).Meanwhile,ursolic acid also induced apoptosis of HCT116^(hSMO)cells in vitro(P<0.05).Furthermore,SC79(Akt activator)enhanced the expressions of p-Akt,GLI1 and c-Myc,which could be abolished by ursolic acid,and the effect was equal to Akt inhibitor LY294002.The expressions of Bcl-2,GLI1,p-Akt,c-Myc,SHH mRNA and proteins were reduced by ursolic acid,while the levels of Bax and SUFU were increased.Ursolic acid could inhibit the growth and induce the apoptosis of colorectal cancer xenograft in vivo.Similarly,lower levels of Bcl-2,GLI1,p-Akt,c-Myc and SHH,and higher expression of Bax and SUFU were noted in ursolic acid-treated mice.CONCLUSION Ursolic acid can inhibit the growth and induce apoptosis of HCT116^(hSMO)cells both in vitro and in vivo.And the mechanism is related to the suppression of PI3K/Akt-mediated noncanonical Hedgehog signaling pathway.
基金National Natural Science Foundation of China(81573813,81173598)Sichuan Provincial Admin⁃istration of Traditional Chinese Medicine of China(2021MS447)+1 种基金Excellent Talent Program of Chengdu University of Tra⁃ditional Chinese Medicine of China(YXRC2019002,ZRYY1917)Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006)。
文摘OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.
基金Project supported by the Natural Science Foundation of Jiangsu Province(BK20151516)the Open Fundation from Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals
文摘The title compound(C(37)H(48)BrNO5, 6) was synthesized from ursolic acid and its crystal structure was determined by single-crystal X-ray diffraction analysis. The compound is of orthorhombic system, space group P212121 with a = 16.846(3), b = 18.844(4), c = 11.262(2)A, Z =4, V = 3575.1(13) A^3, Mr = 666.67, Dc = 1.239 Mg/m^3, S = 1.002, μ = 1.190 mm^-1, F(000) = 1408,the final R = 0.0831 and wR = 0.1459 for 2286 observed reflections(I 〉 2σ(I)). The crystal structure is stabilized by two intermolecular hydrogen bonds(N–H(0A)···O(2) and O(1)–H(1A)···O(3)). In the preliminary antitumor assay, the title compound 6 exhibits potent cytotoxic activity against Hep G2 and SMMC-7721 cells with IC50 values of 1.64 ± 0.21 and 1.22 ± 0.13 μM, respectively.
文摘Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.
文摘The present study reports in vitro anti-sickling activity and phytochemical analyses of the leaves of Ocimum gratissimum.Biological testing revealed that the plant extracts possess antisickling effects.The combination of spectroscopic techniques:1D-NMR,2D-NMR and MS revealed that ursolic acid is the major biologically active compound of O.gratissimum(Silva et al.in Molecules 13:2482–2487,2008;Kedar et al.J Food Drug Anal 20:865–871,2012).This study is the first report of the antisickling activity of ursolic acid isolated from O.gratissimum.The pharmaceutical relevance of findings from this study derives from the possibility of integrating O.gratissimum as an antisickling plant in the pharmacopoeia of Democratic Republic of the Congo.The identification of the active principle could enhance the standardization of antisickling recipe.
基金Science and Technology Innovation Platform Construction Project of Anshun City(ASKP[2017]03)。
文摘[Objectives]This study was conducted to establish a method for determining the contents of Chaenomeles cathayensis(Hemsl.)Schneid.,and analyze the changes in effective components of C.cathayensis grown in Guizhou,so as to provide data support for the production and quality control of C.cathayensis.[Methods]The contents of ursolic acid and oleanolic acid in C.cathayensis in different areas of Guizhou were determined.The HPLC method was adopted under following conditions:chromatographic column waters C18 column(4.6 mm×150 mm,5.0μm);mobile phase:methanol-0.1 mol/L ammonium acetate(85∶15);column temperature:25℃;detection wavelength:257 nm;flow rate 1.0 ml/min.[Results]Through methodological investigations,HPLC could be used to detect the contents of the two terpenoids oleanolic acid and ursolic acid in C.cathayensis from Guizhou.The content of oleanolic acid ranged from 0.076%to 0.144%,and the content of ursolic acid ranged from 0.201%to 0.439%.[Conclusions]A method for determining the contents of C.cathayensis was established using the HPLC method with oleanolic acid and ursolic acid as the index components.The method is accurate,reliable,and simple and easy to implement,and can serve as a reference and support for quality evaluation and standard improvement of C.cathayensis.
文摘<span style="font-family:Verdana;">In the present study, two cell-based systems for assessing Yang and Yin activities were for the first time used to investigate the effect of ursolic acid (UA) and oleanolic acid (OA). The results indicated that while UA was only active in the Yang assay, OA produced activity in the Yin assay. The Yang/Yin activity of UA/OA may be attributed to their distinct molecular structures, which confer their differential ability to interact with mitochondrial membrane or cellular membrane lipids, with resultant membrane fluidization and potentiation of biological responses.</span>
基金supported in part by Grants from National Council for Scientific and Technological Development-CNPq(460184/2014-8),CT-INFRA 2013/FINEP(FINEP 0633/13)Fundacao de AmparoàPesquisa do Estado de Minas Gerais(APQ 02423-18)Federal University of Juiz de Fora.
文摘Lung cancer is the major cause of death in the neoplastic diseases. In spite of the advances in the chemotherapy, the lung cancer treatments are still complex and costly, being necessary the seeking of new drugs. In this context, the ursolic acid (UA) becomes the target of studies that investigate its antitumor potential and, thus, structural modifications can enhance its biological activities. Eight UA semisynthetic derivative compounds (UAD1-8) were synthesized and evaluated their cytotoxic activity against human alveolar adenocarcinoma cells (A549). UAD1, UAD3, UAD5, UAD6 and UAD8 were able to reduce the viability of the A549 cells. Only UAD1 and UAD6 reduced the viability at 24 h, and only UAD3 didn’t reduce the NF-κB expression. The compound UAD1 showed the greater apoptosis induction. Moreover, the compound UAD1 showed better results than UA in all assays. The present study shows, for the first time, the action of these compounds in the apoptotic effect, in the expression of NF-κB and in the A549 cell line. The ursolic acid derivatives showed substantial results in the apoptosis, cytotoxicity and NF-κB inhibition of A549 cells, and further studies are necessary for the development of possible new therapeutic drugs.
基金supported in part by the National Key Research and Development Program of China(No.2022YFC3400501)the National Natural Science Foundation of China(Nos.81825020 and 82150208 to H.L.)+2 种基金the Shanghai Science and Technology Commission Biomedical Science and Technology Support Special Project(Nos.21S11907900 and 20S11901000 to Z.Z.)sponsored by the National Program for Special Supports of Eminent Professionalsthe National Program for Support of Top-Notch Young Professionals.
文摘Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological activities.To clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)fluorophore.Among them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC_(50))=9.21±0.50μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent manner.Then,5c was found to localize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy studies.Preliminary MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and lysosome.In all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.