tannins and Herpes-Simplex

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

Topics: Adhesives; Animals; Antiviral Agents; Cell Line; Chlorocebus aethiops; Female; Herpes Simplex; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Metal Nanoparticles; Mice; Mice, Inbred C57BL; Silver; Simplexvirus; Swine; Tannins

The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

Topics: Animals; Antiviral Agents; Cell Line; Chlorocebus aethiops; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Herpes Simplex; Herpesvirus 2, Human; Inflammation; Metal Nanoparticles; Mice; Microbial Sensitivity Tests; Silver; Tannins; Virus Attachment; Virus Internalization

Casuarinin, a hydrolyzable tannin isolated from the bark of Terminalia arjuna Linn. (Combretaceae), was investigated for its antiviral activity on herpes simplex type 2 (HSV-2) in vitro. Results showed that the IC(50) of casuarinin in XTT and plaque reduction assays were 3.6+/-0.9 and 1.5+/-0.2 microM, respectively. The 50% cytotoxic concentration for cell growth (CC(50)) was 89+/-1 microM. Thus, the selectivity index (SI) (ratio of CC(50) to IC(50)) of casuarinin was 25 and 59 for XTT and plaque reduction assays, respectively. Casuarinin continued to exhibit antiviral activity even added 12 h after infection. During the attachment assay, casuarinin was shown to prevent the attachment of HSV-2 to cells. Furthermore, casuarinin also exhibited an activity in inhibiting the viral penetration. Interestingly, casuarinin was virucidal at a concentration of 25 microM, reducing viral titers up to 100,000-fold. This study concludes that casuarinin possesses anti-herpesvirus activity in inhibiting viral attachment and penetration, and also disturbing the late event(s) of infection.

Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Herpes Simplex; Herpesvirus 2, Human; Hydrolyzable Tannins; Plant Bark; Plants, Medicinal; Tannins; Terminalia; Vero Cells; Viral Plaque Assay; Virion

Water and methanol extracts of 30 traditional medicinal plants, collected in Indonesia, were tested for their anti HSV-1 activity. The extracts of eight plant species showed potent activity on the plaque assay at a concentration of 100 micrograms/mL. The therapeutic efficacy of seven selected plants was demonstrated by using a mouse HSV-1 infection assay, both the methanol extracts of the fruit of Melaleuca leucadendron (Myrtaceae) and the pericarp of Nephelium lappaceum (Sapindaceae) significantly prolonged the development of skin lesions and reduced the mortality.

Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Female; Gallic Acid; Herpes Simplex; Herpesvirus 1, Human; Indonesia; Methanol; Mice; Mice, Inbred BALB C; Plant Extracts; Plants, Medicinal; Solvents; Tannins; Vero Cells; Viral Plaque Assay; Water

Twenty-three male patients with herpes simplex virus type 2 blisters on the prepuce, glans penis, and penile shaft were divided into 2 groups. Ten patients served as controls, and thirteen patients were treated with ultrasound (1 W/cm2 for 60 sec) and Herpigon on 3 consecutive days. Results showed a negative virus culture after 3 days of treatment and significant reduction of the recurrent infection in the treated group while the control group experienced recurrent infection within 62--80 days. This method offers a new therapeutic treatment for genital herpes simplex virus.

Topics: Adult; Drug Combinations; Herpes Simplex; Humans; Hydrolyzable Tannins; Male; Penile Diseases; Semen; Simplexvirus; Tannins; Ultrasonic Therapy; Urea; Zinc

Clinical treatment of 147 female patients suffering with genital herpes simplex virus were conducted in two phases. The purpose of Phase I was to note the efficacy of treatment with ultrasound and Herpigon ointment (zinc, urea, and tannic acid) in relieving pain and shortening the length of time involved in healing. Results indicated that the combined treatment significantly reduced pain and length of healing period. Phase II involved a 2-year follow-up of patients with primary and recurrent infection. Results indicated that the combined treatment significantly reduced recurrent infection in all patients treated.

Topics: Adult; Female; Herpes Simplex; Humans; Hydrolyzable Tannins; Ointments; Recurrence; Tannins; Ultrasonic Therapy; Urea; Uterine Cervicitis; Vulvovaginitis; Zinc

Determination of the effectiveness of chemical treatments for Herpes simplex type 2 infections has generally relied on a reduction in the rate of mortality. A more natural progression of the disease is seen when non-progressive cutaneous lesions are induced. Treatment of characteristic cutaneous lesions with ultrasound alone, a cream compound designated Herpigon alone, or a combination of ultrasound and Herpigon were compared to determine the time required for lesions to heal and the amount of virus recoverable from treated lesions. Results indicate that the use of Herpigon alone or in combination with ultrasound resulted in a significant reduction in the time required for the lesions to heal. A comparison of the amount of virus present in treated lesions indicated that the combined treatment was most effective in reducing the amount of recoverable virus.

Topics: Animals; Guinea Pigs; Herpes Simplex; Hydrolyzable Tannins; Male; Ointments; Tannins; Ultrasonic Therapy; Urea; Zinc

Twenty-three male patients with herpes simplex virus type 2 blisters on the prepuce, glans penis, and penile shaft were divided into two groups. Ten patients served as controls, and thirteen patients were treated with ultrasound (1 watt/cm2 for 60 seconds) and Herpigon on three consecutive days. Results showed a negative virus culture after three days of treatment and significant reduction of recurrent infection in the treated group while the control group experienced recurrent infection within 62-80 days. This method offers a new therapeutic treatment for genital herpes simplex virus.

Topics: Adult; Animals; Guinea Pigs; Herpes Simplex; Humans; Hydrolyzable Tannins; Male; Ointments; Tannins; Ultrasonic Therapy; Urea; Zinc

Topics: Adenoviridae; Amnion; Antiviral Agents; Culture Techniques; Feces; Herpes Simplex; Humans; Poliovirus; Salmonella Phages; Salmonella typhimurium; Tannins; Virus Diseases; Viruses