ABSTRACT
Rosa cymosa Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of R. cymosa fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of R. cymosa fruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150 µg/mL) triggered apoptosis by 26.52-83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44-58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets of R. cymosa against hematologic cancer cells suggested its potential application as an antileukemic dietary supplement.
Subject(s)
Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Ethanol/chemistry , PTEN Phosphohydrolase/metabolism , Plant Extracts/pharmacology , Rosa/chemistry , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Damage , Endoplasmic Reticulum Stress/drug effects , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , Mice, SCID , Mitochondria/drug effects , Mitochondria/metabolism , NF-E2-Related Factor 2/metabolism , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Sequestosome-1 Protein/metabolism , Signal Transduction , Xenograft Model Antitumor AssaysABSTRACT
Two new lanostanoids, 3α-acetoxy-22-oxo-5α-lanosta-8,24-dien-21-oic acid, named tsugaric acid D (1) and 16α-hydroxy-3-oxo-5α-lanosta-6,8,24(24(1))-trien-21-oic acid, named tsugaric acid E (2) were isolated from the fruit bodies of Ganoderma tsugae. The structures 1 and 2 were determined by spectroscopic methods. Compound 1 and known compounds 3 and 6 exhibited significant inhibitory effects on xanthine oxidase (XO) activity with an IC50 values of 90.2±24.2, 116.1±3.0, and 181.9±5.8 µM, respectively. Known compound 5 was able to protect human keratinocytes against damage induced by UVB light, which showed 5 could protect keratinocytes from photodamage. The 1 and 5 µM 1 combined with 5 µM cisplatin, respectively, enhanced the cytotoxicity induced by cisplatin. It suggested that 1 and 5 µM 1 combined with low dose of cisplatin may enhance the therapeutic efficacy of cisplatin and reduce side effect and cisplatin resistant.
Subject(s)
Antioxidants/therapeutic use , Biological Products/therapeutic use , Ganoderma/chemistry , Keratinocytes/drug effects , Lanosterol/analogs & derivatives , Prostatic Neoplasms/drug therapy , Xanthine Oxidase/antagonists & inhibitors , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/pharmacology , Biological Products/chemistry , Biological Products/pharmacology , Cisplatin/pharmacology , Cisplatin/therapeutic use , Fruiting Bodies, Fungal/chemistry , Herb-Drug Interactions , Humans , Inhibitory Concentration 50 , Keratinocytes/radiation effects , Lanosterol/chemistry , Lanosterol/isolation & purification , Lanosterol/pharmacology , Lanosterol/therapeutic use , Male , Molecular Structure , Phytotherapy , Radiation Injuries, Experimental/drug therapy , Skin Diseases/prevention & controlABSTRACT
Two new triterpenoids, garcinielliptones Q (1) and S (3), and a new phloroglucinol, garcinielliptone R (2), were isolated from the seed of Garcinia subelliptica. Their structures were established by analysis of their spectroscopic data. Phloroglucinol, garcinielliptone FC (4) from this plant exhibited a significant increase of antiproliferative effect, while 4 combined with cisplatin significantly caused decrease of cell inhibition induced by cisplatin in NTUB1. Exposure of NTUB1 cells to 4 cotreated with cisplatin for significantly decreased the amount of reactive oxygen species (ROS) than that of the total amount generated by 4 and cisplatin. These results suggested that 4 could protect the cisplatin toxicity through reduction of ROS in NTUB1. Phloroglucinols, garcinielliptones, A (5) and F (7), and garsubelline A (6), from this plant, revealed ABTS radical cation scavenging activity and 5 displayed an inhibitory effect on xanthine oxidase. These finding showed that 5-7 may be used as antioxidants.
Subject(s)
Antioxidants/pharmacology , Cytotoxins/pharmacology , Garcinia/chemistry , Plant Extracts/pharmacology , Antioxidants/analysis , Antioxidants/isolation & purification , Cell Death/drug effects , Cell Line, Tumor , Cytotoxins/analysis , Cytotoxins/isolation & purification , Humans , Plant Extracts/analysis , Plant Extracts/isolation & purification , Seeds/chemistryABSTRACT
Bioassay-guided fractionation of stems of Engelhardia roxburghiana led to isolation of: four diarylheptanoids, engelheptanoxides A-D (1-4); two cyclic diarylheptanoids, engelhardiols A (5) and B (6); one naphthoquinone dimer, engelharquinonol (7); and one 1-tetralone, (4S)-4,6-dihydroxy-1-tetralone (8), along with 24 known compounds (9-32). The structures of 1-8 were by spectroscopic analysis. Compounds 5, 6, 13, 22, and 23 showed antitubercular activity against Mycobacterium tuberculosis H(37)Rv with MIC values of 72.7, 62.1, 9.1, 15.3, and 70.1µM, respectively.
Subject(s)
Antitubercular Agents/metabolism , Antitubercular Agents/pharmacology , Juglandaceae/metabolism , Plant Extracts/metabolism , Plant Extracts/pharmacology , Plant Stems/metabolism , Antitubercular Agents/chemistry , Juglandaceae/chemistry , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Plant Extracts/chemistry , Plant Stems/chemistryABSTRACT
A known triterpenoid, ß-amyrin (1), and a known and a new phloroglucinol, cohulupone (2) and garcinielliptone P (3), were isolated from the pericarp and heartwood and seed of Garcinia subelliptica, respectively. A new xanthonolignoid, hyperielliptone HF (4), was isolated from the heartwood of Hypericum geminiflorum. The new compounds were established by analysis of their spectroscopic data. Compounds 1-3 showed an inhibitory effect on xanthine oxidase (XO). Treatment of NTUB1, a human bladder cancer cell, with 1 or 1 cotreated with cisplatin for 24 h resulted in a decreased viability of cells. Exposure of NTUB1 to 1 or 1 cotreated with cisplatin for 24 h significantly increased the level of production of reactive oxygen species (ROS). Flow cytometric analysis indicated that treatment of NTUB1 with 1 or 1 cotreated with cisplatin led to the cell cycle arrest, accompanied by an increase in the extent of apoptotic cell death in 1 or 1 combined with cisplatin-treated NTUB1 after 24 h. These data suggested that the presentation of cell cycle arrest and apoptosis in 1 or 1 combined with cisplatin-treated NTUB1 for 24 h was mediated through an increased amount of ROS in cells exposed to 1 or 1 cotreated with cisplatin.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Garcinia/chemistry , Oleanolic Acid/analogs & derivatives , Phloroglucinol/pharmacology , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cisplatin/pharmacology , Down-Regulation , Humans , Oleanolic Acid/pharmacology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/physiopathology , Xanthine Oxidase/antagonists & inhibitorsABSTRACT
A new phloroglucinol, hyperielliptone HA (1/1a), a new spirophloroglucinol possessing an unprecedented skeleton, hyperielliptone HB (2/2a), and two new xanthonolignoids, hyperielliptones HC (3) and HD (4), were isolated from the heartwood of Hypericum geminiflorum. Compounds 1/1a and 2/2a were obtained as tautomeric pairs. The structures and relative configurations of these compounds were elucidated by spectroscopic methods. In biological testing, compound 2/ 2a revealed significant inhibition of oxidative DNA damage and an inhibitory effect on xanthine oxidase.
Subject(s)
Antioxidants , Free Radical Scavengers , Hypericum/chemistry , Phloroglucinol , Plants, Medicinal/chemistry , Xanthine Oxidase/antagonists & inhibitors , Algorithms , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/pharmacology , DNA Damage/drug effects , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/pharmacology , Molecular Structure , Phloroglucinol/analogs & derivatives , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Phloroglucinol/pharmacology , Stereoisomerism , Taiwan , Xanthine Oxidase/metabolismABSTRACT
A new phloroglucinol, garcinielliptone HF ( 1), possessing an unprecedented skeleton, and the tautomeric pair of garcinielliptone FC ( 2/ 2a) were isolated from the heartwood and pericarp of Garcinia subelliptica, respectively. Their structures, including relative configurations, were elucidated by means of spectroscopic methods. The ability of compounds 1 and 2/ 2a to induce DNA-cleavage activity was examined using supercoiled plasmid pBR322 DNA. In the presence of Cu(II), compounds 1 and 2/ 2a caused significant breakage of pBR322 DNA. The involvement of H2O2 and O2 (*-), and H2O2, O2 (*-), and OH (*) in 1- and 2/ 2a-mediated scission, respectively, was established by inhibition or no protection of DNA breakage by various oxygen radical scavengers. Thus, in the presence Cu(II), 1 and 2/ 2a may show a prooxidant effect on DNA and induce cell death.