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.