OBJECTIVE: JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis. METHODS: HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay. RESULTS: HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001). CONCLUSION JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.
Caspase 1/metabolism* ; Inflammasomes/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Simplexvirus/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Herpes Simplex/drug therapy* ; Humans

The study investigated the inhibitory effect and mechanism of tectorigenin derivative(SGY) against herpes simplex virus type Ⅰ(HSV-1) by in vitro experiments. The cytotoxicity of SGY and positive drug acyclovir(ACV) on African green monkey kidney(Vero) cells and mouse microglia(BV-2) cells was detected by cell counting kit-8(CCK-8) method, and the maximum non-toxic concentration and median toxic concentration(TC_(50)) of the drugs were calculated. After Vero cells were infected with HSV-1, the virulence was determined by cytopathologic effects(CPE) to calculate viral titers. The inhibitory effect of the tested drugs on HSV-1-induced cytopathy in Vero cells was measured, and their modes of action were initially explored by virus adsorption, replication and inactivation. The effects of the drugs on viral load of BV-2 cells 24 h after HSV-1 infection and the Toll-like receptor(TLR) mRNA expression were detected by real-time fluorescence quantitative PCR(RT-qPCR). The maximum non-toxic concentrations of SGY against Vero and BV-2 cells were 382.804 μg·mL~(-1) and 251.78 μg·mL~(-1), respectively, and TC_(50) was 1 749.98 μg·mL~(-1) and 2 977.50 μg·mL~(-1), respectively. In Vero cell model, the half maximal inhibitory concentration(IC_(50)) of SGY against HSV-1 was 54.49 μg·mL~(-1), and the selection index(SI) was 32.12, with the mode of action of significantly inhibiting replication and directly inactivating HSV-1. RT-qPCR results showed that SGY markedly reduced the viral load in cells. The virus model group had significantly increased relative expression of TLR2, TLR3 and tumor necrosis factor receptor-associated factor 3(TRAF3) and reduced relative expression of TLR9 as compared with normal group, and after SGY intervention, the expression of TLR2, TLR3 and TRAF3 was decreased to different degrees and that of TLR9 was enhanced. The expression of inflammatory factors inducible nitric oxide synthase(iNOS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) was remarkably increased in virus model group as compared with that in normal group, and the levels of these inflammatory factors dropped after SGY intervention. In conclusion, SGY significantly inhibited and directly inactivated HSV-1 in vitro. In addition, it modulated the expression of TLR2, TLR3 and TLR9 related pathways, and suppressed the increase of inflammatory factor levels.
Animals ; Antiviral Agents/therapeutic use* ; Chlorocebus aethiops ; Herpes Simplex/pathology* ; Herpesvirus 1, Human/metabolism* ; Isoflavones ; Mice ; TNF Receptor-Associated Factor 3/pharmacology* ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 3/metabolism* ; Toll-Like Receptor 9/metabolism* ; Toll-Like Receptors/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Vero Cells ; Virus Replication

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.
Animals ; Capsules ; Herpes Simplex ; Herpesvirus 1, Human ; Mice ; Mice, Inbred BALB C ; Psychological Distress

ABSTRACT The symptoms of recurrent oral herpes infection may vary, from mild discomfort to life threatening. Dentists are more likely to be consulted in this oral infection, hence the ability to diagnose and treat this disease is mandatory. This article described manifestation and therapy of recurrent oral herpes infection. In the first case, a 41-year-old woman came with a complaint of painful sore mouth in her lower gingiva. She experienced canker sores for two to three times a year on the tongue, lips and palate. Laboratory results showed positive IgM anti HSV-2, which matched with the primary herpes infection. However, based on the history and clinical manifestations, she was diagnosed with recurrent intra oral herpes infection. In the second case, a 70-year-old man came with a very painful canker sores in his entire mouth. The patient had to be hospitalised for three days and received analgesic, antibiotic and gel containing triamcinolone. After hospitalisation, canker sores did not heal. Extraorally, we found a crust in the vermillion border of the upper lip and intraorally, we found multiple ulceration of keratinised and non-keratinised mucosa. The use of topical steroid in this patient may aggravated ulceration due to its ability to cause rapid spreading of the virus. The first patient was given chlorhexidine gluconate 0.2% and the second patient was prescribed with doxycycline rinse. Both patients received multivitamin containing zinc. Complete history taking, objective and adjunctive examination played a role in establishing the diagnosis and treatment of recurrent oral herpes infections.
Stomatitis, Herpetic

No abstract available.
Herpes Simplex ; Simplexvirus ; Skin Diseases

Atopic dermatitis is a common chronic, relapsing skin disorder, and many patients with atopic dermatitis use complementary and alternative medicine instead of consulting a certified dermatologist. Herein, we report the case of a 38-year-old woman with severe eczema herpeticum who had been treated with herbal medicine and acupuncture for her atopic dermatitis. Herbal medicine and acupuncture are the most frequent types of alternative medicine that Korean patients rely on. However, the effectiveness of these treatments in atopic dermatitis remains unclear as there is a great lack of scientific evidence supporting it. As atopic dermatitis can cause potentially fatal secondary infections such as eczema herpeticum, dermatologists should put great effort into communicating with and educating the patients and in guiding them to choose the most appropriate treatment plan for managing their atopic dermatitis.
Acupuncture ; Adult ; Coinfection ; Complementary Therapies ; Dermatitis, Atopic ; Eczema ; Female ; Herbal Medicine ; Humans ; Kaposi Varicelliform Eruption ; Skin

BACKGROUND: Mutation in the gene encoding filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD), in association with distinct features such as increased allergic sensitization, higher severity, and frequent skin infections. Genetic diversity in FLG mutations exists across ethnicities. OBJECTIVE: This study aimed to investigate the clinical features of AD according to the presence of FLG mutation in Korean individuals. METHODS: We performed reverse blot hybridization assay to detect FLG mutation in Korean patients with AD. Classifying subjects into AD with or without FLG mutation, clinical features of AD and patch test results were compared between the two groups. RESULTS: Among a total of 281 subjects, 39 (13.9%) were found to have FLG mutation. AD with FLG mutation was associated with higher risk of impetigo and eczema herpeticum but lower risk of prurigo nodularis. In the patch test, there was no difference in positive reactions of major contact allergens between the groups. CONCLUSION: In Korean patients with AD, FLG mutation was associated with more frequent skin infections but not with personal or family history of atopic diseases, allergic sensitization, contact allergy, and protracted course. It is important to consider other skin-barrier-related genes, such as KLK7 and SPINK5, and immune response-related genes in conjunction.
Allergens ; Causality ; Dermatitis, Atopic ; Genetic Variation ; Humans ; Hypersensitivity ; Impetigo ; Kaposi Varicelliform Eruption ; Patch Tests ; Prurigo ; Skin

No abstract available.
Cytomegalovirus ; Herpes Simplex ; Humans ; Retinitis

We report a case of congenital cytomegalovirus and Herpes simplex virus infection suspected via ultrasound indicated by the presence of fetal cerebral abnormalities. The pregnancy was electively terminated at 31 weeks of gestation. The postmortem examination of the foetus showed brain with lissencephaly. The histopathological examination revealed numerous enlarged cells containing cytomegalic inclusions and multinucleated giant cells in multiple fetal organs and placenta. Documented evidence of histopathological detection of cytomegalovirus inclusions in multiple organs are very sparse in literature. This case highlights the causal relationship of viral infections in early pregnancy and abnormalities of the central nervous system.
Cytomegalovirus ; Herpes simplex virus

BACKGROUND: Kaposi varicelliform eruption (KVE) is a disseminated viral infection primarily caused by the herpes simplex virus in the setting of an underlying chronic skin disease. Few studies have reported the clinical characteristics and predisposing factors for recurrent KVE.OBJECTIVES: To characterize the clinical features and predisposing factors for recurrent KVE.METHODS: This retrospective comparative study of recurrent vs. single-episode KVE was performed at the Pusan National University Hospital between 2004 and 2017.RESULTS: A total of 84 episodes occurred in 60 patients, and of these, 13 patients developed recurrence (21.7%). No statistically significant intergroup difference was observed in the mean age and sex distribution. The face was the most common site of involvement in both groups, followed by the trunk and the upper and lower extremities. Atopic dermatitis was the most common pre-existing disease in both groups; however, Darier's disease was more common in the recurrent KVE group, and this difference was statistically significant. Most patients with KVE (66.7%) showed aggravation of the underlying skin disease within 3 months of KVE onset. This finding was more prominent in patients with recurrent episodes (91.7%) than in those with single-episode KVE (58.3%), (p=0.040).CONCLUSION: This study can contribute to a better understanding of recurrent KVE and guide clinicians in treating patients with conditions predisposing to KVE.
Busan ; Causality ; Darier Disease ; Dermatitis, Atopic ; Humans ; Kaposi Varicelliform Eruption ; Lower Extremity ; Preexisting Condition Coverage ; Recurrence ; Retrospective Studies ; Sex Distribution ; Simplexvirus ; Skin Diseases