phenanthrenes and Hyperplasia

The discovery of new therapeutic drugs with the efficacious and safe ability to prevent epidermal hyperplasia is extremely urgent for psoriasis. Cryptotanshinone (CTS), an active component isolated from the root of Salvia miltiorrhiza Bunge, has been reported to have antibacterial and antitumor effects. However, its effects on psoriasis have not been reported. Here, we investigated the therapeutic effects of CTS on imiquimod (IMQ)-induced psoriatic-like skin model and explored the underlying mechanisms. Our results revealed that CTS effectively alleviates IMQ-induced epidermal hyperplasia. In vitro studies also indicated that CTS potently inhibits the growth of keratinocytes. We further found that STAT3, a transcription factor for the cell growth, is the key mediator of CTS on the proliferation of keratinocytes. Taken together, our findings indicated that the curative effects of CTS on psoriasis are accomplished mainly through modulating STAT3, which providing evidences to develop CTS as a potential therapeutic agent for patients with psoriasis.

Topics: Animals; Cell Line; Cell Proliferation; Disease Models, Animal; Drugs, Chinese Herbal; Epidermis; Humans; Hyperplasia; Imiquimod; Keratinocytes; Male; Mice, Inbred C57BL; Phenanthrenes; Psoriasis; STAT3 Transcription Factor

Topics: Administration, Topical; Animals; Cricetinae; Hyperplasia; Mesocricetus; Phenanthrenes; Sebaceous Gland Diseases; Sebaceous Glands

We have reported that triptolide inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether suppresses airway remodeling and goblet cell hyperplasia, studied the mechanism of triptolide on mucin5ac (Muc5ac) expression in a murine model of asthma.. BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by repetitive ovalbumin challenge for 6 weeks. Treatments included triptolide (40 μg/kg) and dexamethasone (2mg/kg). The area of bronchial airway (WAt/Pbm), smooth muscle (WAm/Pbm) and mucus index were assessed 24h after the final OVA challenge. Levels of Muc5ac were assessed by ELISA, immunohistology and real-time PCR. Western blot was performed to analyze the phosphorylation of NF-κB p65.. Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway, smooth muscle and goblet cell hyperplasia. Levels of lung Muc5ac and Muc5ac mRNA were significantly reduced in mice treated with triptolide and dexamethasone. Phosphorylation of NF-κB p65 was significantly reduced in mice treated with triptolide and dexamethasone.. Triptolide may inhibit airway goblet cell hyperplasia and Muc5ac expression in asthmatic mice via NF-κB. It may be a potential drug for the treatment of patients with severe asthma.

Topics: Airway Remodeling; Animals; Asthma; Blotting, Western; Bronchi; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Diterpenes; Epoxy Compounds; Female; Goblet Cells; Hyperplasia; Hypertrophy; Mice, Inbred BALB C; Mucin 5AC; Mucus; NF-kappa B; Phenanthrenes; Phosphorylation; RNA, Messenger; Transcription Factor RelA

To investigate the effect of tashinone IIA (TA) on intimal hyperplasia in a rat model of carotid artery balloon injury and on the proliferation of cultured vascular smooth muscle cells (VSMCs) induced by fetal bovine serum (FBS) and its underlying mechanisms.. Carotid artery injury was induced in rats by balloon dilatation and they were treated with TA or vehicle for 2 weeks until killed for assessment of neointimal formation and lumen area. VSMC was cultured in vitro and proliferation was assessed by determining cell number, bromodeoxyuridine (BrdU) incorporation and cell cycle analysis. The extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and c-fos expression were assessed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) respectively.. TA could significantly decrease intimal thickening, suppress cell proliferation and BrdU incorporation into DNA, block cell cycle in G(0)/G(1) phase, inhibit ERK1/2 phosphorylation and c-fos expression.. TA abolishes VSMC proliferation and reduces intimal hyperplasia through inhibition of mitogen-activated protein kinase (MAPK) signaling pathway and down-regulation of c-fos expression.

Topics: Abietanes; Angioplasty, Balloon; Animals; Bromodeoxyuridine; Carotid Arteries; Carotid Artery Injuries; Cell Culture Techniques; Cell Cycle; Cell Proliferation; DNA; Extracellular Signal-Regulated MAP Kinases; Hyperplasia; Male; MAP Kinase Signaling System; Muscle, Smooth, Vascular; Phenanthrenes; Phosphorylation; Plant Extracts; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Salvia miltiorrhiza; Tunica Intima

To test the effect of Tanshinone II A nanoparticles on the expression of MMP-2.. Thirty five male New Zealand white rabbits were randomly divided into three groups. In group A (15 rabbits), the carotid arteries of the rabbits were stripped. In group B (5 rabbits) and C (15 rabbits), nanoparticles and Tanshinone II A nanoparticles were perfused respectively in the denudated arteries of the rabbits. The neointimal areas and the IOD values of MMP-2 secretion were measured.. A significant reduction of neointimal hyperplasia in group C was found compared to the other two groups in terms of the intimal area and the intima-media ratio. Group C had significant lower IOD values than group A.. Local administration of nanoparticles with incorporated Tanshinone I A not only inhibits neointimal hyperplasia but also inhibits the expression of MMP-2 in stripped arteries.

Topics: Abietanes; Animals; Carotid Arteries; Drugs, Chinese Herbal; Hyperplasia; Male; Matrix Metalloproteinase 2; Nanoparticles; Phenanthrenes; Rabbits

Tanshinone IIA nanoparticles were constructed and perfused in rabbit's right carotid after intimal denudation with ballon. Localization and retention at different time points of the coumarin-labeled drug nanoparticles were evaluated under laser confocal microscope. Nanoparticles were seen in the three layers of the cross-section artery. At 7 days, they were mainly deposited in the medial layer, while the deposition was generally observed in the adventitia and media at 14 days and 28 days. In the Tanshinone IIA nanoparticle study, a significant reduction of the neo-intimal hyperplasia was noted by comparing the intimal area and the intima-media ratio in the three groups. And the PLGA nanoparticles appeared to be fully biocompatible. As a result, the local administration of the nanoparticles with incorporated Tanshinone IIA showed not only the preventive effects, but aslo the high absorption and good biocompatability in the whole arterial wall.

Topics: Abietanes; Angioplasty, Balloon; Animals; Caprolactam; Carotid Arteries; Drug Carriers; Hyperplasia; Lactic Acid; Nanoparticles; Phenanthrenes; Polyesters; Polymers; Rabbits; Tunica Intima

To study the preventive effect of Sodium Tanshinone II A sulfonic acid on intimal hyperplasia in rabbit iliac artery balloon injury model and explore the possible mechanism.. Thirty male pure hreed New Zealand white rabbits were undertaken experimental balloon injury in left iliac artery. Then the rabbits were assigned into treatment group (n=15) and control group (n=15), paired with weights. Sodium Tanshinone II A sulfonic acid had been injected intravenously with 7.5 - 9 mg/day for 6 days in treatment group. Saline of equivalence was given in contol group. The balloon injured arteries were harvested in the 7th, 14th, and 28th days after balloon injuy, and Paraffin sections were made. At last, HE staining, apoptosis TUNEL assay were undertaken.. (1) HE staining analysis: Media and intimal areas in treatment group at 14th day post-operation were larger than that in the 7th day (P = 0.003 and < 0.001, respectively). Media and intimal areas in treatment group decreased at the 28th day post-operation, while increased in control. Both media and intimal areas were significantly different (P < 0.001 respectively. (2) Tunel analysis discovered that, apoptosis reached peak in both treatment and control groups at the 28th post-operation. Differences of apoptosis cells counts in media and intimal between treatment and control groups were non-significant at the 7th, and 28th days, while differences at the 14th day were significant(p = 0.031 and 0.029 respectively). Apoptosis cells counting in treatment group at the 14th day increased more dramatically than that in the control.. Intravenous Sodium Tanshinone II A sulfonic acid inhibites intimal proliferation after arterial balloon injury in rabits. The effect can e partially explaineArte by the induction of apoptosis in injured artery. Clinical effect of tanshinone II A still needs further evaluation. Sodium TA-II A sulfonic acid may be of potential therapeutic value in the prevention of. To study the preventive effect of Sodium Tanshinone II A sulfonic acid on intimal by perplasia in rabbit iliac artery balloon injury model and explore the possible mechanism.. Thirty male pure breed Nexw Zealand white rabbits were un-dertaken experimental balloon injury in left iliac artery. Then the rabbits were assigned into treatment group (n=15) and control group (n=15), paired with weights. Sodium Tanshinone II A sulfonie acid had been injected intraxenously with 7.5 - 9 mg/day for 6 days in treatment group. Saline of equivalence was given in contol group. The balloon injured arteries were harvested in the 7th, 14th, and 28th days after balloon injury, and Paraffin sections were made. At last, HE staining, apoptosis TUNEL assay were undertaken.. (1) HE staining analysis: Media and intimal areas in treatment group at 14th day post-operation were larger than that in the 7th day (P = 0.003 and < 0.001, respectively). Media and intimal areas in treatment group decreased at the 28th day post-operation, while increased in control. Both media and intimal areas were significantly different (P < 0.001 respectively. (2) Tunel analysis discovered that, apoptosis reached peak in both treatment and control groups at the 28th post-operation. Differences of apoptosis cells counts in media and intimal between treatment and control groups were non-significant at the 7th, and 28th days, while differences at the 14th day were significant (p = 0.031 and 0.029 respectively). Apoptosis cells counting in treatment group at the 14th day increased more dramatically than that in the control.. Intravenous Sodium Tanshinone II A sulfonic acid inhibites intimal proliferation after arterial balloon injury in rabbits. The effect can he partially explained by the induction of apoptosis in injured artery. Clinical effect of tanshinone II A still needs further evaluation. Sodium TA-II A sulfonic acid may be of potential therapeutic value in the prevention of restenosis after angioplasty.

Topics: Abietanes; Animals; Apoptosis; Catheterization; Disease Models, Animal; Drugs, Chinese Herbal; Hyperplasia; Iliac Artery; Injections, Intravenous; Male; Phenanthrenes; Plants, Medicinal; Rabbits; Sulfonic Acids; Tunica Intima; Tunica Media

Vascular smooth muscle cell (VSMC) proliferation is considered to play a central role in the development of intimal hyperplasia with pathological artery healing. Danshen, the Salvia miltiorrhiza Bge., has long been regarded as an effective traditional Chinese medicine for cardiovascular diseases. In this paper, the effects of tanshinone (TA), the lipid-soluble pharmacological constituents of danshen, on the intima hyperplasia and proliferating state of VSMC were described in a mouse carotid artery injured by complete cessation of blood flow. This study showed that oral administration of TA could significantly decrease the intimal thickening of injured vessels and proliferating cell nuclear antigen (PCNA)-positive VSMC in intimal area. These results suggested that the suppressive effects of TA on intimal hyperplasia might partly result from its inhibitory effect against VSMC proliferation.

Topics: Abietanes; Animals; Anticoagulants; Carotid Arteries; Female; Hyperplasia; Mice; Muscle, Smooth, Vascular; Phenanthrenes; Proliferating Cell Nuclear Antigen; Tunica Intima

To observe the preventive and therapeutic effect of tanshinone (TA) on artery restenosis in mice and primarily explore the mechanism.. Female KM mice were randomly divided into model control, low dose and high dose TA groups. Each group had 12 mice. The low and high dose drug groups were respectively given TA 3 and 6 g x kg(-1) x d(-1) by ig; the model control group was given the same volume solvent. The controlateral carotid of ligated artery of model control group was regarded as normal control. 2 days later, the mice' s left common carotid artery was dissected and ligated near the carotid bifurcation, leading to intima hyperplasia and then establishing restenosis model. 4 weeks later, the artery was harvested and stained by hematoxylin-elsin (HE) and immunohistochemistry of PCNA. The morphological changes were checked under microscope; the area of the intimal and medial layer of the vessels, and their ratios were analyzed with image analysis software. The expression level of PCNA was expressed as the positive index.. Compared with those of normal artery, the intimal area, media area and intima-to-media ratio of ligated artery increased obviously (P < 0.01). But TA could significantly decrease all of these parameters (P < 0.01), and also decrease the positive index of PCNA (P < 0.01).. TA effectively inhibits intima hyperplasia, which is mainly characterized with the proliferation and migration of smooth muscle cell induced by abnormal hemodynamic changes. This result suggestes that TA may play a positive role in the prevention of restenosis after PTCA.

Topics: Abietanes; Animals; Anticoagulants; Carotid Arteries; Carotid Stenosis; Dose-Response Relationship, Drug; Female; Hyperplasia; Ligation; Mice; Phenanthrenes; Plants, Medicinal; Proliferating Cell Nuclear Antigen; Random Allocation; Recurrence; Salvia miltiorrhiza; Tunica Intima

A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Abietanes; Animals; Anticarcinogenic Agents; Antioxidants; Arachidonic Acid; Benzo(a)pyrene; Dermatitis, Contact; DNA; Drug Interactions; Enzyme Induction; Epidermis; Female; Hyperplasia; Magnoliopsida; Mice; Mice, Inbred Strains; Ornithine Decarboxylase; Phenanthrenes; Plant Extracts; Skin; Skin Neoplasms; Spices; Tetradecanoylphorbol Acetate; Triterpenes; Tritium; Ursolic Acid

The histopathogenesis of rat forestomach carcinoma induced experimentally with aristolochic acid was investigated. The intragastric administration of 10 mg/kg/day caused extensive necrosis of the squamous epithelium, followed by regeneration and hyperplasia, papilloma formation and ultimately by invasive squamous cell carcinoma.

Topics: Animals; Antineoplastic Agents; Aristolochic Acids; Hyperplasia; Male; Neoplasms, Experimental; Papilloma; Phenanthrenes; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms

In an effort to establish a test system to examine the carcinogenic potential of chemicals, mouse prostate explants were maintained as organ cultures and the effects of carcinogenic and noncarcinogenic compounds were examined at various intervals after treatment. The degree of hyperplasia produced by a compound was determined by the colcemid metaphase arrest technique. Extensive hyperplasia of the prostatic epithelium occurred at 8 days after treatment with 3-methylcholanthrene, the 11-12 epoxide of methylcholanthrene, benzo(a)pyrene and N-methyl-N-nitro-N-nitrosoguanidine. At 12 days most carcinogen-treated explants were anaplastic. The noncarcinogenic compounds, pyrene and phenanthrene, did not produce a mitotic stimulatory effect on the epithelium of the explants. The data suggest that the organ culture system of mouse prostate may be employed as a test system to obtain preliminary information regarding the cardinogenicity of a compound.

Topics: Anaplasia; Animals; Benzopyrenes; Carcinogens; Epithelium; Ethers, Cyclic; Hyperplasia; Male; Methylcholanthrene; Methylnitronitrosoguanidine; Mice; Mitosis; Organ Culture Techniques; Phenanthrenes; Prostate; Pyrenes

Topics: Aniline Compounds; Animals; Anthracenes; Azo Compounds; Benz(a)Anthracenes; Benzopyrenes; Carcinogens; Cystadenoma; Epithelial Cells; Epithelium; Female; Hyperplasia; Kidney; Kidney Neoplasms; Kidney Tubules; Maternal-Fetal Exchange; Mice; Mice, Inbred Strains; Organ Culture Techniques; Phenanthrenes; Polycyclic Compounds; Pregnancy; Stimulation, Chemical