ABSTRACT
A further chemical investigation of the bulbs of Bessera elegans (Liliaceae) led to the isolation of a new homoisoflavonoid (1), a new scillascillin-type homoisoflavonoid (2), three known flavonoids (3-5), and two known norlignans (6 and 7). The structures of the new homoisoflavonoids (1 and 2) were determined based on the results of extensive spectroscopic analysis, including two-dimensional NMR data. The isolated compounds (1-7) were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and TIG-3 normal human diploid fibroblasts. Compound 1 exhibited potent tumor-selective cytotoxic activity against HL-60 cells.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Isoflavones/isolation & purification , Liliaceae/chemistry , HL-60 Cells , Humans , Isoflavones/chemistry , Isoflavones/pharmacologyABSTRACT
Examination of the bulbs of Bessera elegans (Liliaceae) led to isolation of nine new and five known steroidal glycosides. The structures of the nine compounds were determined based on the results of spectroscopic analysis, including two-dimensional NMR, and hydrolysis followed by chromatographic and spectroscopic analysis. The isolated compounds and derivatives were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human diploid fibroblasts. One compound, the pseudo-furostanol glycoside, induced apoptosis in HL-60 and A549 cells in a time-dependent manner and cell-cycle arrest at the G0/G1 phase in A549 cells.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Glycosides/isolation & purification , Glycosides/pharmacology , Liliaceae/chemistry , Steroids/isolation & purification , Steroids/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Cell Cycle Checkpoints , Drug Screening Assays, Antitumor , Glycosides/chemistry , HL-60 Cells , Humans , Japan , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistry , Steroids/chemistry , SterolsABSTRACT
CONCLUSIONS: The endolymphatic sac (ES) is important for inner ear fluid homeostasis. A dysfunctional ES can cause vertigo attacks following additional stress such as a sudden change in endolymphatic volume and/or pressure, or restricted inner ear blood flow. OBJECTIVE: The purpose of this study was to elucidate the mechanism of vertigo attacks in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were given an intratympanic injection of lipopolysaccharide and an intraperitoneal injection of aldosterone. These 'model' animals had epinephrine or sodium nitroprusside (SNP) instilled into the middle ear cavity. Cochleae, vestibules, and endolymphatic sacs were studied morphologically by light microscopy. RESULTS: The injection of epinephrine into the model animals reduced the endolymphatic hydrops in the cochlea, but also produced mild hydrops in the vestibule, which was never observed in untreated (control) animals. The ES did not react to epinephrine in the normal way. Injection of SNP did not cause any changes.
Subject(s)
Ear, Inner/drug effects , Ear, Inner/pathology , Meniere Disease/pathology , Animals , Disease Models, Animal , Ear, Inner/blood supply , Epinephrine/pharmacology , Injections , Meniere Disease/chemically induced , Mice , Mice, Inbred CBA , Microscopy , Nitroprusside/pharmacology , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/pharmacologyABSTRACT
CONCLUSION: It is suggested that transient receptor potential vanilloid (TRPV)-1 and -2 may be of pathological significance for sensory cells and ganglions, while TRPV-3 and -4 may play an important part in neuroprotection of the inner ear. OBJECTIVE: Changes in the expression of TRPV-1, -2, -3, and -4 in gentamicin (GM)-treated mouse inner ear were studied. MATERIALS AND METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear of both untreated and GM-treated CBA/J animals (intratympanic injection of 5 mg GM) was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co-expressed in the inner ear sensory and ganglion cells, while TRPV-4 was also expressed in the stria vascularis and vestibular dark cells. Following GM treatment, the intensity of immunofluorescent reaction to TRPV-1 and TRPV-2 increased, while that to TRPV-3 and TRPV-4 decreased.
Subject(s)
Anti-Bacterial Agents/toxicity , Calcium Channels/analysis , Ear, Inner/drug effects , Gentamicins/toxicity , TRPV Cation Channels/analysis , Aldehydes/analysis , Animals , Brain-Derived Neurotrophic Factor/analysis , Ear, Inner/pathology , Ganglia, Spinal/drug effects , Ganglia, Spinal/pathology , Hair Cells, Auditory, Inner/drug effects , Hair Cells, Auditory, Inner/pathology , Hair Cells, Auditory, Outer/drug effects , Hair Cells, Auditory, Outer/pathology , Mice , Mice, Inbred CBA , Microscopy, Fluorescence , Nerve Fibers/drug effects , Nerve Fibers/pathology , Organ of Corti/drug effects , Organ of Corti/pathology , Semicircular Ducts/drug effects , Semicircular Ducts/pathology , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/pathology , Spiral Ganglion/drug effects , Spiral Ganglion/pathology , Stria Vascularis/drug effects , Stria Vascularis/pathology , Trigeminal Ganglion/drug effects , Trigeminal Ganglion/pathology , Tyrosine/analogs & derivatives , Tyrosine/analysis , Vestibular Nerve/drug effects , Vestibular Nerve/pathologyABSTRACT
CONCLUSION: It is suggested that transient receptor potential vanilloids (TRPVs) may play a functional role in cell physiology and TRPV-4 and -2 may play an important part in fluid homeostasis in the inner ear. OBJECTIVE: Expression of TRPV-1, -2, -3, and -4 in the normal mouse inner ear was studied. MATERIALS AND METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic sac, was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co-expressed in hair cells and supporting cells of the organ of Corti, in spiral ganglion cells, sensory cells in vestibular end organs, vestibular ganglion cells, and sensory nerve fibers. TRPV-2 was also detected in the stria vascularis, dark cells, and endolymphatic sac. TRPV-4 was expressed in hair cells and supporting cells of the organ of Corti, in marginal cells of the stria vascularis, spiral ganglion cells, vestibular sensory cells, vestibular dark cells, vestibular ganglion cells, and epithelial cells of the endolymphatic sac.
Subject(s)
Ear, Inner/metabolism , Hearing , Postural Balance , TRPV Cation Channels/metabolism , Animals , Mice , Mice, Inbred CBAABSTRACT
CONCLUSIONS: That the endolymphatic sac (ES) reacts to changes in inner ear blood flow may be important for homeostasis of the inner ear fluid volume and pressure. OBJECTIVES: To elucidate the effect of changes in inner ear blood flow on the ES and to learn more about the volume and pressure regulatory function of the ES. MATERIALS AND METHODS: Epinephrine or sodium nitroprusside (SNP) was injected into the middle ear cavity of adult CBA/J mice. The ES were analyzed morphologically by light microscopy. RESULTS: Epinephrine reduced the luminal size of the ES leading to an accumulation of intraluminal homogeneous substance. Injection of SNP increased the size of the ES lumen, accompanied by a collapse of the lateral intercellular space (LIS) and dense perisaccular tissue. These changes were almost reversed 4 h after injection.
Subject(s)
Ear, Inner/blood supply , Endolymphatic Sac/cytology , Animals , Cochlea/blood supply , Endolymphatic Duct/cytology , Endolymphatic Duct/drug effects , Endolymphatic Sac/drug effects , Endolymphatic Sac/physiology , Epinephrine/pharmacology , Mice , Mice, Inbred CBA , Nitroprusside/pharmacology , Regional Blood Flow/drug effects , Stria Vascularis/cytology , Stria Vascularis/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/pharmacologyABSTRACT
CONCLUSIONS: Homeostasis of endolymph volume is a complex mechanism, in which the endolymphatic sac (ES) may play an important role. OBJECTIVES: To elucidate the effect of acute endolymphatic hydrops (EH) on the ES and to gain further information about the volume and pressure regulative function of the ES. MATERIALS AND METHODS: Distilled water was injected into the middle ear cavity of adult CBA/J mice. The ESs were studied morphologically by light and transmission electron microscopy. RESULTS: Mild EH was found, particularly in the upper turn of the cochlea. Acute EH led to an increase in the size of the ES lumen, accompanied by collapse of the lateral intercellular spaces and dense perisaccular tissue, changes which had reversed 2 h after the injection.
Subject(s)
Endolymphatic Hydrops/pathology , Endolymphatic Sac/pathology , Acute Disease , Animals , Cochlea/pathology , Cochlear Duct/ultrastructure , Extracellular Space/physiology , Homeostasis/physiology , Mice , Mice, Inbred CBA , Microscopy, Electron, TransmissionABSTRACT
CONCLUSION: A new murine model for the study of Ménière's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine.
