Recent Advances in the Discovery of Novel Anti-Herpetic Agents from Chinese Herbal Medicines

C.      L. Cheng; K.      Y. Ng; H.      X. Xu

doi:10.2174/138527210792927690

Abstract

Many Chinese herbs have been tested against herpes simplex virus (HSV) in search for new anti-herpetic agents. Extracts and novel molecules such as polysaccharides, tannins, terpenes, lignans, saponins, lectins and flavonoids have been found to be effective as anti-herpetic agents. Using different in vitro and in vivo models, novel compounds isolated from Chinese herbal medicines (CHM) have been tested and demonstrated with strong inhibitory effects on HSV through different mechanisms. CHM like Camellia sinensis, Mentha piperita, Myrica rubra, Pterocarya stenoptera, Smilax glabra and Terminalia arjuna are effective even at early stage of HSV infection to hinder viral attachment and penetration. Other CHM including Chamaecyparis obtuse, Glycyrrhiza glabra, Lobelia chinesis and Ocimum basilicum are capable of interfering in viral replication. Nelumbo nucifera, Pithecellobium clypearia, Polygonum cuspidatum and Schefflera heptaphylla have been reported to block host cellular machineries while Plantago major and Prunella vulgaris have shown to induce immunomodulatory effect. It is also noticeable that some CHM showed dual and even multiple roles in combating HSV infection. Structural modifications of CHM derived compounds by changing the degree of sulfation and oxygenation, transforming specific moiety, addition of chemical groups and increasing molecular weight resulted in enhanced anti-herpetic activity with high selectivity and low toxicity. It is a hopeful attempt to develop topical microbicides which possess multiple actions on the early or late stage of HSV infections from CHM. In this review, we focus on the promising results and the working mechanisms on the anti-herpetic activities of several CHM and the potential of their clinical applications.

Keywords: Chinese herbal medicines, herpes simplex virus, HSV-1, HSV-2, structural modification, microbicides, Anti-Herpetic Agents, polysaccharides, tannins, terpenes, lignans, saponins, flavonoids, Myrica rubra, Pterocarya stenoptera, Smilax glabra, transforming specific moiety, encephalitis, meningitis, corneal blindness, neonatal infections, skin lesions, mucocutaneous herpes, guanosine nucleoside, viral DNA polymerase, Acyclovir (ACV), Mutations, thymidine kinase, anti-HSV chemotherapy, cyclin-dependent kinases, oxidation process, Chamaecyparis Obtusa, Euphorbia Jolkini, Euphorbia Thymifolia, virucidal effect, heteroannular diene structure, Lobelia Chinensis, Melia Azedarach, herpetic stromal keratitis, mitogen-activated, protein kinase cascades, Mentha Piperita, non-cytotoxic concentrations, Morus Alba, anti-herpetic mechanism, bioassay-guided fractionation, Ocimum Basilicum, Phyllanthus Urinaria, Geraniin, galloyltricetifavan, cellular proteins, Plantago Major, Polygonatum Cyrtonema, Polygonum Cuspidatum, virus replication, Prunella Vulgaris, lignin-carbohydrate complex, macrophage-related cytokines, TNF-a, IL-1b, IL-6, Schefflera Heptaphylla, fetuin-binding glycoprotein (SGPF2), viral infection, lupeol, Terminalia Arjuna, Typhonium Divaricatum, single drug, ACV, drug-resistant viral strains, therapeutic HSV vaccine, Sodium rutin sulfate, cross-linking, HSV inhibition, topical microbicides