Herbal medicinal products in herpes virus diseases
In-vitro and in-vivo activity of crude herbal extracts
The search for natural antivirals was actually initiated by the Boots drug company (UK) in 1952. Since then many broad-based screening programmes have been undertaken throughout the world to evaluate the in-vitro and in-vivo antiviral activity of plant extracts and many of them revealed strong antiherpes virus activity, while some can be used as a lead for the development of antiherpes virus agents. These reviews report the in-vitro and sometimes in-vivo antiherpes virus activities of many plant extracts, mainly against HSV-1 and HSV-2.
Garlic (Allium sativum) extracts showed strong inhibitory activity against HCMV. Interestingly the intraperitoneal administration of black seed (Nigella sativa) oil to BALB/c mice strikingly inhibited HCMV in-vitro murine cytomegalovirus (CMV) titres in spleen and liver (Salem and Hossain, 2000) while the extract of Terminalia chebula not only significantly inhibited herpes simplex virus in vivo, but also the replication of HCMV in vitro and murine CMV in immunosuppressed mice.
Canadian researchers first reported the antiviral activities of grape, apple and strawberry juices against herpes simplex virus and other viruses; while leaf extract of Azadirachta indica inhibited DNA viruses. British Columbian ethnomedicines Cardamine angulata, Conocephalum conicum, Polypodium glycyrrbiza showed anti-HSV-1 activity; while strong anti-HSV activity was found with Byrsonima verbascifolia extract, a folk remedy for skin infections. The aqueous extracts of Nepeta nepetella, Dittricbia viscosa and Sanguisorba minor magnolii of the Iberian peninsula inhibited vesicular stomatitis virus (VSV) and HSV-1 at 50-125 Lig/mL; while the Nepalese ethnomedicine Nerium indicum inhibited herpes simplex virus and influenza A virus. The Chinese antipyretic and anti-inflammatory folk medicine Rheum officinale and Paeonia suffruticosa prevented herpes simplex virus attachment and penetration. Senecio ambavilla, a folk remedy of La Reunion Island, had anti-HSV-1 and anti-poliovirus activities. The extracts of Aglaia odorata, Moringa oleifera and Ventilago denticulate, folk medicines of Thailand, inhibited thymidine kinase-deficient and phosphonoacetate-resistant HSV-1 and delayed the development of skin lesions at 750 mg/kg per dose, increased the mean survival times and reduced the mortality of infected mice similar to acyclovir. The Taiwanese folk remedy Boussingaultia gracilis and Serissa japonica extract was shown to inhibit herpes simplex virus and adenoviruses (ADV) 3, 8 and 11.. Interestingly the viral adsorption, replication and transcription of HSV-1 and HSV-2 were inhibited by Ceratostigma willmattianum extract, an ethnomedicine of China, with IC50 of 29.46 and 9.2 mg/L respectively.
The extracts of Senna petersiana, a folk remedy for sexually transmitted diseases, have strong anti-HSV activity. The aqueous extract of Carissa edulis (Forssk.) Vahl (Apocynaceae) root from Kenya, significantly (100%) inhibited plaque formation in Vero E6 cells infected with 100 PFU of wild-type herpes simplex virus or resistant herpes simplex virus strains at 50 µg/mL in vitro with minimal cell cytotoxicity (CC50 480 µg/mL). The extract at an oral dose of 250 mg/kg significantly (50%) delayed the onset of herpes simplex virus infections in a murine model using Balb/C mice, cutaneously infected with wild-type or resistant strains of herpes simplex virus.
Methanol and hot-aqueous extracts of 25 different plant species, used in Yemeni traditional medicine when tested in two in-vitro viral systems using HSV-1 in Vero cells and influenza virus A in MDCK cells, showed greater activity against HSV-1 at non-cytotoxic concentrations.
In-vitro and in-vivo antiherpetic activity of compounds from herbal extracts
A list of some potential herbal extracts along with the isolated compounds having antiherpes virus activities with probable mode of action are presented in Table Important antiherpetic extracts and compounds from diverse chemical groups.
Table Important antiherpetic extracts and compounds from diverse chemical groups
| Natural product | Source | Antiviral activity (lg/mL) | |
| Whole extract | Aglaria odorata | HSV-1 | |
| Moringa oleitfera | |||
| Ventilago dentitculata | |||
| Boussingaultia gracilis | HSV-1, HSV-2 | ||
| Serissa japonitca | |||
| Cretastitgma willmaltianum | HSV-1 (9.12, 36.5) | ||
| Senna petersitana | HSV-1 | ||
| Triphasia trifolia | HSV-1, HSV-2 | ||
| Artocarpus lakoocha | |||
| Millettia erythrocalyx | HSV | ||
| Caritssa edulis | HSV-1, HSV-2 (50) | ||
| Geranium sanguitneum | HSV-1, HSV-2 (3.6-6) | ||
| Propolis | HSV-1, VZV, HSV-2 | ||
| Alkaloids | |||
| Cepharanthine | Stephania cepharantha | HSV | |
| FK-3000 | Stephania cepharantha | HSV-1 (7.8) | |
| Harmine | Ophiorrhiza nicobarica | HSV-2 (300) | |
| Bis-benzylisoquinoline | |||
| Protoberberine | Stephania cepharantha Hayata | HSV-1 (18) | |
| N-methylcrotsparine | HSV-1, HSV-2 (7.8-9.9) (90, 71, 81) | ||
| Phenolics | |||
| Caffeic acid | Plantago major | HSV-1 (15.3), VZV | |
| P. major | HSV-2 (87.3) | ||
| Chlorogenicacid | Aloe barbadensits | HSV-1 (47.6) | |
| HSV-2 (86.5) | |||
| Procyanidin A1 | Vaccinium vittits-itdaca | HSV-2 | |
| Procyanidin C1 | Crataegus sitnaitca | HSV-1 | |
| Prodelphinidine-o-gallate | Myrica rubra | HSV-2 (5.3) | |
| Rosmarinicacid | Plantago major | VZV | |
| Xanthohumol | Humulus lupulus | HSV | |
| Polyphenols | Geranium sanguitneum L | HSV-1, HSV-2 (3.6-6.2) | |
| Cochinolide B, tremulacin | Homalium cochinchinensis | HSV-1.HSV-2 | |
| Asiaticoside | Centella asitatitca | HSV | |
| Mangiferin | Mangifera tnditca | HSV-1, HSV-2 | |
| Rutin, rutin sulphate | — | HSV-1 (3-8.8) | |
| Phenolics | Rheum officinale | HSV-1 | |
| Paeonia suffrutitcosa | HSV-1 | ||
| Melia toosendan | HSV-1 | ||
| Flavonoitds | |||
| Catechin | Citrus aurantium, Vittits vitnitfera | HSV-1 | |
| Hesperidin | Orange, grape | HSV | |
| Resveratrol | — | HSV | |
| Oxyresveratrol | Millettia erythrocalyx | HSV | |
| Quercetin | Caesalpinia pulcherritma | HSV-1 (24.3), (20) | |
| Phloroglucinol methyl gallate | Mallotus japonicus | HSV | |
| Apigenin | Ocimum basillicum | HSV-1 | |
| Epiafzelechin | Cassia javanica | HSV-2 | |
| Terpenes/sterols | |||
| Betulinic acid | Ocitmum basilicum, Rhusjavanitca | HSV (2.6) | |
| Isoborneol | Melaleuca alternifolia | HSV-1, 2(0.06) | |
| Lupenone | Euphorbia segetalits | HSV-1, HSV-2 | |
| Moronic acid | Myrceugenia euosma, R. javanitca | HSV (3.9), HSV-2 | |
| Glycyrrhetinic acid | Glycyrrhitzitn glabra | HSV-1 | |
| Pulegone | Minthostachys verticil lata | HSV-1 (10) | |
| Putranjivain A | Euphorbia jolkini | HSV-2, (6.3 μM) | |
| Ursolic acid | — | HSV-1 | |
| Sclerocarpic acid (sesquiterpene) | Glyptopetalum sderocarpum | HSV-1, HSV-2 | |
| Scopadulcicacid B (diterpenoid) | Scoparia duicits L. | HSV-1 (16.7) | |
| Morin | Madura cochitnchitnensis | HSV-2 (38.5-53) | |
| Quassinoids | — | EBV | |
| 28-deacetylsendanin (Limonoid) | Melia azedarach | HSV-1(1.46) | |
| Meliacine | Melia azedarach | HSV-1 | |
| Asiaticoside | Centella asitatitca L. | HSV-1, HSV-2 | |
| Mangiferin | Mangifera tnditca L. | HSV-1, HSV-2 | |
| Cochinolide B, tremulacin | Homalitum cochitnchitnensis | HSV-1 , HSV-2 | |
| Essential oil | Minthostachys verticillata | HSV | |
| Artemisia arborescen | HSV-2 | ||
| Black seed oil | Nigella satitva | MCMV | |
| N-N-B5 | Nelumbo nucitfera | HSV-1, HSV-2 (50-62) | |
| Thiazolylsulphonamide | — | HSV | |
| n-docosanol | — | HSV-1 | |
| Oryzacystatin | Oryzae satitva | HSV-1 | |
| Saponins | |||
| 8-Acetylharpagide, scorodioside | Bupleurum nitgidum | HSV-1 (500) | |
| Saikosaponin | Scrophularita scorodonita | VSV | |
| Saponin glycosides (spirostane, tomatidane) | Solanum spp. | HSV-1 | |
| Tannin | |||
| Casuarinin | Terminalia arjuna | HSV-2(1.5 μM) | |
| Eugeniin | Geum japonitcum | HSV-1, HSV-2, EBV | |
| Syzygitum aromatitcum | HSV, VZV | ||
| Samaragenin B | Limonitum sitnensit | HSV-1 | |
| Ellagitannins | Phyllanthus myrtitfolius, P. urinaria | EBV | |
| Euglobal-G1,G2,G3 | Eucalyptus grandits | EBV | |
| n-docosanol | HSV-1 | ||
| Lignans | |||
| Lignan | Rhus javanitca | HSV-2 | |
| Yatein | Chamaecyparits obtusa | HSV-1 | |
| Carbohydrate | |||
| Polysaccharide | Selerotium glucanitcum | HSV-1 | |
| Anionic polysaccharide | Prunella vulgaris | HSV-I(100), HSV-2(10) | |
| Polysaccharide lignan complex | Prunella vulgaris | HSV-1, HSV-2 (20—100) | |
| Sulphated galactans | Bostrychia montagneit | HSV | |
| Galactofucan | Undaria pitnnatitda | HSV-1, HSV-2 | |
| Proteins and peptides | |||
| Mannose-specific lectins | Listera ovata | CMV (0.08) | |
| GlcNAc) n-specific lectin | Urtica dioica | CMV (0.3—9) | |
| Peptide | Sorghum bitcolor | HSV-1 | |
HSV = herpes simplex virus; VZV = varicella zoster virus; CMV = cytomegalovirus; MCMV = murinecytomegalovirus; EBV = Epstein-Barr virus.
