naphthoquinones and Chronic-Disease

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a plant-derived naphthoquinones obtained mainly from three families, including Plumbaginaceae, Droseraceae, and Ebenaceae. Plumbagin has exhibited its potential therapeutic benefits on numerous chronic diseases, i.e., breast cancer, non-small cell lung cancer, melanoma, ovarian, squamous cell carcinomas, pancreatic cancer, and prostate cancer. In addition, its anti-inflammatory and antimicrobial activities as well as control of diabetes and cardiovascular diseases have been reported. Thus, plumbagin is a promising agent for development as a new drug for the treatment or control of chronic diseases. Studies on controlled drug release or drug delivery systems have been involved for improvement of its therapeutic efficacy as well as for the reduction of its toxicity. However, most of the recent research information is from in vitro and in vivo studies. Further clinical studies are therefore required for its developments and applications as a novel drug used to treat chronic diseases.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Cardiovascular Agents; Chronic Disease; Drug Discovery; Humans; Hypoglycemic Agents; Molecular Structure; Naphthoquinones; Phytotherapy; Plants, Medicinal; Signal Transduction

Shikonin is a naphthoquinone compound extracted from the root of Lithospermum with various pharmacological activities. Sympathetic neural remodeling greatly contributes to chronic heart failure. Growing evidence has identified a critical role of microRNAs (miRNAs) in a variety of cardiac biological processes. This study aimed to verify whether shikonin could attenuate sympathetic neural remodeling and explore the possible regulatory role of miRNAs in this process.. Shikonin was administered to mice after transverse aortic constriction (TAC). Immunohistochemistry and western blotting were used to assess the expression of TAC-induced sympathetic remodeling-related proteins.. TAC-induced expression of the sympathetic remodeling-related proteins, tyrosine hydroxylase (TH), growth associated protein 43 (GAP43), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and nerve growth factor (NGF), was significantly decreased in cardiac tissues. MiR-124 expression significantly increased after heart failure and decreased after shikonin treatment. An adeno-associated virus 9 (AAV9) vector was packaged and used to transfect myocardial tissues of aortic-constricted mice with miR-124, resulting in increased heart miR-124 levels and inhibition of the effects of shikonin on sympathetic neural remodeling. Immunohistochemical staining showed that the density of TH-, GAP43-, and ChAT-positive nerves was significantly increased in aortic-constricted mice after transfection with AAV9-miR-124.. Our data demonstrate that shikonin administration prevents sympathetic neural remodeling in mice with TAC-induced heart failure. The effects of shikonin on heart failure may be partly due to miR-124-mediated attenuation of sympathetic remodeling. Our results reveal a novel mechanism underlying the therapeutic effect of shikonin in heart failure.

Topics: Animals; Cardiotonic Agents; Chronic Disease; Constriction, Pathologic; GAP-43 Protein; Gene Expression Regulation; Heart Failure; Male; Mice, Inbred C57BL; MicroRNAs; Myocardium; Naphthoquinones; Sympathetic Nervous System; Vesicular Acetylcholine Transport Proteins

To test the hypothesis that chronic hypoxic pulmonary hypertension (CH-PH) is associated with increased survivin and decreased voltage-gated potassium (KV) channels expression in pulmonary arteries, rats were randomized as: normoxia (N); normoxia + YM155, survivin suppressor (NY); hypoxia (H); hypoxia + YM155 (HY). HY group had significantly reduced pulmonary arterial pressure, right ventricular weight and right ventricular hypertrophy compared with H group. Survivin mRNA and protein were detected in pulmonary arteries of rats with CH-PH, but not rats without CH-PH. YM155 downregulated survivin protein and mRNA. KV channel expression and activity were upregulated after YM155 treatment. Survivin may play a role in the pathogenesis of CH-PH.

Topics: Animals; Chronic Disease; Disease Models, Animal; Gene Expression Regulation; Hypertension, Pulmonary; Hypoxia; Imidazoles; Male; Microtubule-Associated Proteins; Muscle, Smooth, Vascular; Naphthoquinones; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Pulmonary Wedge Pressure; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA; Survivin

The hydroxynaphthoquinone, atovaquone (Wellvone, Glaxo-Wellcome Ltd.) was found to have significant activity against Babesia microti, the main cause of human babesiosis in the U.S.A. This activity compares well with that of the most effective babesicide currently available for use in animals, imidocarb dipropionate, that unlike atovaquone is not licensed for use in humans. Treatment with well tolerated doses of atovaquone results in a rapid reduction in parasitemias and an early disappearance of parasites from blood smears. However, in common with all the other babesicides tested, atovaquone did not sterilize gerbils of infection, even at very high daily doses administered for up to 10 days. A combination of atovaquone and clindamycin was more effective than atovaquone alone in the treatment of both acute and chronic infections but failed to eliminate parasites completely.

Topics: Acute Disease; Animals; Antiprotozoal Agents; Atovaquone; Babesiosis; Chronic Disease; Clindamycin; Diminazene; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Gerbillinae; Humans; Imidocarb; Naphthoquinones; Pentamidine; Recurrence

To evaluate the effects of drug therapy on the clinical course of acute acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts present in the brain and ocular tissues in the hamster animal model.. The Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In acute disease, systemically administered atovaquone was compared with conventional therapies (pyrimethamine combined with sulfadiazine; clindamycin; and spiramycin). The clinical course of the ocular disease was determined with retinal examination and photography of the fundus. The number of Toxoplasma cysts remaining after treatment was evaluated in aliquots of brain homogenate and in retinal tissue. The effect of atovaquone on cerebral Toxoplasma cyst count was also studied in chronic disease.. None of the drugs administered altered the course of the acute disease, judged by clinical examination. Atovaquone alone significantly reduced the number of cerebral Toxoplasma cysts after acute disease. Atovaquone also significantly reduced the cerebral Toxoplasma cyst count in chronic disease.. Tissue cysts are believed to be responsible for reactivation of Toxoplasma retinochoroiditis. Atovaquone has the potential to reduce the risk of recurrent disease.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Atovaquone; Brain; Chorioretinitis; Chronic Disease; Cricetinae; Disease Models, Animal; Drug Therapy, Combination; Female; Mesocricetus; Naphthoquinones; Retina; Toxoplasma; Toxoplasmosis, Cerebral; Toxoplasmosis, Ocular

The aim of this work was to develop a new pharmaceutical form of atovaquone and to study its activity against Toxoplasma gondii in vitro and in vivo. Nanocapsules were chosen as the oral dosage form of administration. An analytical method was developed to determine the drug content in nanocapsules. The stability of these nanocapsules were assessed by following drug content, size, pH and osmolarity for a period of six months. The in vitro activity of atovaquone-loaded nanocapsules against tachyzoites of T. gondii (RH stain) was comparable to its suspension form. In vivo studies were carried out in murine models of acute and chronic toxoplasmosis. Mice acutely infected with the virulent RH strain were orally treated with a dose regimen of 15 mg/kg/day for 10 days, starting from day 1 post-infection. 75% of the mice receiving atovaquone-loaded nanocapsules survived 30 days post-infection, compared to none of untreated controls and none of mice treated with the suspension with the same dose regimen. In mice chronically infected by the COUL or the ME49 strain (Type II strains), then treated for six weeks, treatment with atovaquone (15 mg/kg/d, nanoparticles or suspension) resulted in a decrease of brain parasitic burden, which was significantly more pronounced in ME49-infected mice and in those treated with drug-loaded nanocapsules. These results show that the sensibility of T. gondii to atovaquone is different according to the strains and that the activity of atovaquone in the treatment of toxoplasmosis is enhanced when administered in nanoparticular form.

Topics: Acute Disease; Administration, Oral; Animals; Antiprotozoal Agents; Atovaquone; Brain; Capsules; Chronic Disease; Colloids; Disease Models, Animal; Drug Carriers; Drug Stability; Female; Lung; Mice; Naphthoquinones; Parasitemia; Solubility; Survival Rate; Suspensions; Temperature; Toxoplasma; Toxoplasmosis, Animal

Lymphotropic therapy with trental was administered to patients with chronic herpetic stomatitis. Trental was injected near the mastoid process after preinjection with lidase (total dose no more than 1 ml on each side, 6 sessions per course). The treatment normalized the immune status, clinical symptoms regressed sooner than after treatment with an antiviral agent bonafton, remissions were prolonged, and in 5 out of 18 patients no more relapses occurred.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Antibody Formation; Antiviral Agents; Chronic Disease; Drug Therapy, Combination; Humans; Hyaluronoglucosaminidase; Immunity, Cellular; Immunity, Innate; Injections, Intralymphatic; Naphthoquinones; Pentoxifylline; Stomatitis, Herpetic

The morphological effects of drug treatment with atovaquone in the brains of mice chronically infected with Toxoplasma gondii was examined by light and electron microscopy. As early as 1 and 2 weeks of treatment there appeared to be fewer tissue cysts compared to untreated controls and this reduction was more significant after 4 weeks treatment. There also appeared to be a decrease in the number of inflammatory nodules and the severity of the meningitis. Ultrastructurally, the cysts of both treated and control animals were located within host cells. There was a marked increase in both the number of cysts with lysed bradyzoites and the number of degenerate bradyzoites after 4 weeks treatment. It is probable that the drug is more active against the metabolically active immature bradyzoites than the mature organisms. Drug treatment does not appear to result in rupture of tissue cysts or release of Toxoplasma antigens since there is a reduction rather than an increase in the inflammatory response. This drug may be useful in treating chronic toxoplasmosis since it appears to be active against the bradyzoites reducing the parasite burden (cyst number) without initiating a destructive inflammatory response.

Topics: Animals; Antiprotozoal Agents; Atovaquone; Brain; Chronic Disease; Female; Mice; Mice, Inbred CBA; Microscopy, Electron; Naphthoquinones; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral

Transcription of type 1 human immunodeficiency virus (HIV-1) provirus is governed by the viral long terminal repeat (LTR). Drugs can block HIV-1 replication by inhibiting activity of its LTR. We report that topotecan, beta-lapachone, and curcumin are potent and selective inhibitors of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells. At these concentrations, each drug inhibited p24 antigen production in cells either acutely or chronically infected with HIV-1. Their target is transcriptional function of the LTR.

Topics: Acute Disease; Antiviral Agents; Camptothecin; Cells, Cultured; Chronic Disease; Curcumin; Gene Expression Regulation, Viral; HIV Infections; HIV Long Terminal Repeat; HIV-1; In Vitro Techniques; Naphthoquinones; RNA, Viral; Topotecan; Virus Replication