Novel series of limonin derivatives （V-A-I-V-A-8, V-B-I-V-B-8） were synthesized by adding various tertiary amines onto the C （7）-position of limonin. The synthesized compounds possessed favorable physicochemical p...Novel series of limonin derivatives （V-A-I-V-A-8, V-B-I-V-B-8） were synthesized by adding various tertiary amines onto the C （7）-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound V-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.展开更多
In this paper, it was aimed to identified and quantified hesperidin and limonin compounds using HPLC （High Performance Liquid Chromatography） techniques against to developing of mal secco disease caused by Phoma tra...In this paper, it was aimed to identified and quantified hesperidin and limonin compounds using HPLC （High Performance Liquid Chromatography） techniques against to developing of mal secco disease caused by Phoma tracheiphila. Six citrus lemon varieties （Meyer, Kiitdiken, Enterdonato, Yediveren, Sweet lemon and Euroka） were infected by P. tracheiphila and artificial inoculation were applied in vivo conditions. Before and after inoculation, leaf, branch and stem samples were taken from each lemon varieties. The results show that the amount of hesperidin and limonin concentration was increased after the inoculations at various levels based on the lemon cultivars. Various concentrations （1, 5, 10, 25, 50, 75, 100 ppm） of hesperidin and limonin compounds were also tested under in vitro conditions to compare response of P. tracheiphila development. According to the results, hesperidin and limonin compounds play an important role against to P. tracheiphila development and Sweet Lemon variety was found to be the most resistance both observation and HPLC results.展开更多
BACKGROUND Limonin is one of the most abundant active ingredients of Tetradium ruticarpum.It exerts antitumor effects on several kinds of cancer cells.However,whether limonin exerts antitumor effects on colorectal can...BACKGROUND Limonin is one of the most abundant active ingredients of Tetradium ruticarpum.It exerts antitumor effects on several kinds of cancer cells.However,whether limonin exerts antitumor effects on colorectal cancer(CRC)cells and cancer stem-like cells(CSCs),a subpopulation responsible for a poor prognosis,is unclear.AIM To evaluate the effects of limonin on CSCs derived from CRC cells.METHODS CSCs were collected by culturing CRC cells in serum-free medium.The cytotoxicity of limonin against CSCs and parental cells(PCs)was determined by cholecystokinin octapeptide-8 assay.The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability.RESULTS As expected,limonin exerted inhibitory effects on CRC cell behaviors,including cell proliferation,migration,invasion,colony formation and tumor formation in soft agar.A relatively low concentration of limonin decreased the expression stemness hallmarks,including Nanog andβ-catenin,the proportion of aldehyde dehydrogenase 1-positive CSCs,and the sphere formation rate,indicating that limonin inhibits stemness without presenting cytotoxicity.Additionally,limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice.Moreover,limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression.Inhibition of Nanog andβ-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2μmol/L colievlin.CONCLUSION Taken together,these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.展开更多
Limonin, the main bioactive phytochemical constituent of limonoids with multi-functions, is enriched in citrus fruits and often found at a high concentration in citrus seeds. The present study was attempted to introdu...Limonin, the main bioactive phytochemical constituent of limonoids with multi-functions, is enriched in citrus fruits and often found at a high concentration in citrus seeds. The present study was attempted to introduce a new and efficient extraction method to isolate limonoids from pummelo seeds, and to evaluate the antioxidant property of the main constituent limonin in Hep G2 cells. Three key single factors were identified for the extraction of limonoids from pummelo seeds using the Box-Behnken experiment design of response surface methodology(RSM), and the optimized extraction parameters were treatment with 89.68 m L of anhydrous acetone for 4.62 h at 78.94C, while the yield of limonoids was 11.52 mg/g. The structure of isolated main constituent of the limonoids was further identified as limonin by Fourier transform infrared(FT-IR) spectrometer and nuclear magnetic resonance(NMR)spectrum. Moreover, the molecular data in Hep G2 cells revealed that limonin exerted its anti-oxidant property mainly by the activation of nuclear factor(erythroid-2)-like 2(Nrf2)/kelch-like ECHassociated protein 1(Keap1)-antioxidant response element(ARE) pathway in the form of transcriptional regulation of Nrf2 m RNA and posttranscriptional regulation of Nrf2/Keap1 system. These results demonstrate that pummelo seeds are an ideal source of limonoids, and limonin is proved to exert its anti-oxidant property by the activation of Nrf2/Keap1 pathway.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.21472242)the National Science and Technology Major Project for "Significant New Drugs Creation" of China(Grant No.2015ZX09102001)State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMZZCX201406)
文摘Novel series of limonin derivatives （V-A-I-V-A-8, V-B-I-V-B-8） were synthesized by adding various tertiary amines onto the C （7）-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound V-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.
文摘In this paper, it was aimed to identified and quantified hesperidin and limonin compounds using HPLC （High Performance Liquid Chromatography） techniques against to developing of mal secco disease caused by Phoma tracheiphila. Six citrus lemon varieties （Meyer, Kiitdiken, Enterdonato, Yediveren, Sweet lemon and Euroka） were infected by P. tracheiphila and artificial inoculation were applied in vivo conditions. Before and after inoculation, leaf, branch and stem samples were taken from each lemon varieties. The results show that the amount of hesperidin and limonin concentration was increased after the inoculations at various levels based on the lemon cultivars. Various concentrations （1, 5, 10, 25, 50, 75, 100 ppm） of hesperidin and limonin compounds were also tested under in vitro conditions to compare response of P. tracheiphila development. According to the results, hesperidin and limonin compounds play an important role against to P. tracheiphila development and Sweet Lemon variety was found to be the most resistance both observation and HPLC results.
文摘BACKGROUND Limonin is one of the most abundant active ingredients of Tetradium ruticarpum.It exerts antitumor effects on several kinds of cancer cells.However,whether limonin exerts antitumor effects on colorectal cancer(CRC)cells and cancer stem-like cells(CSCs),a subpopulation responsible for a poor prognosis,is unclear.AIM To evaluate the effects of limonin on CSCs derived from CRC cells.METHODS CSCs were collected by culturing CRC cells in serum-free medium.The cytotoxicity of limonin against CSCs and parental cells(PCs)was determined by cholecystokinin octapeptide-8 assay.The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability.RESULTS As expected,limonin exerted inhibitory effects on CRC cell behaviors,including cell proliferation,migration,invasion,colony formation and tumor formation in soft agar.A relatively low concentration of limonin decreased the expression stemness hallmarks,including Nanog andβ-catenin,the proportion of aldehyde dehydrogenase 1-positive CSCs,and the sphere formation rate,indicating that limonin inhibits stemness without presenting cytotoxicity.Additionally,limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice.Moreover,limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression.Inhibition of Nanog andβ-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2μmol/L colievlin.CONCLUSION Taken together,these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.
基金partially supported by Natural Science Foundation of China(31101268)Core Research Program 1515 of Hunan Agricultural University of China to Si Qin
文摘Limonin, the main bioactive phytochemical constituent of limonoids with multi-functions, is enriched in citrus fruits and often found at a high concentration in citrus seeds. The present study was attempted to introduce a new and efficient extraction method to isolate limonoids from pummelo seeds, and to evaluate the antioxidant property of the main constituent limonin in Hep G2 cells. Three key single factors were identified for the extraction of limonoids from pummelo seeds using the Box-Behnken experiment design of response surface methodology(RSM), and the optimized extraction parameters were treatment with 89.68 m L of anhydrous acetone for 4.62 h at 78.94C, while the yield of limonoids was 11.52 mg/g. The structure of isolated main constituent of the limonoids was further identified as limonin by Fourier transform infrared(FT-IR) spectrometer and nuclear magnetic resonance(NMR)spectrum. Moreover, the molecular data in Hep G2 cells revealed that limonin exerted its anti-oxidant property mainly by the activation of nuclear factor(erythroid-2)-like 2(Nrf2)/kelch-like ECHassociated protein 1(Keap1)-antioxidant response element(ARE) pathway in the form of transcriptional regulation of Nrf2 m RNA and posttranscriptional regulation of Nrf2/Keap1 system. These results demonstrate that pummelo seeds are an ideal source of limonoids, and limonin is proved to exert its anti-oxidant property by the activation of Nrf2/Keap1 pathway.
