Botanical Treatment Strategies for Herpes: Antiviral Botanicals

2013

The following herbs represent a selection of botanicals used for internal and / or topical antiviral therapy. All have shown some measure of antimicrobial activity in various studies and are a promising area of research for herpes treatment. Specific studies of the effects of herbs on herpes simplex virus are presented in the following. These herbs may be used singly, but more commonly are used by herbal practitioners in combination with other antivirals, or in comprehensive, multiherb, multieffect formulae.

Aloe

Aloe has long been used by herbalists as a topical healing agent for wounds, burns, irritated skin, and sores. Two studies were conducted by Syed et al. examining the efficacy of topical aloe vera treatments on men experiencing primary outbreaks of genital herpes. In the first study, 120 men were randomized into three parallel groups receiving either 0.5% in hydrophilic cream, aloe vera gel, or placebo three times daily for 2 weeks. The shortest mean duration of healing occurred with aloe vera cream, followed by gel and then placebo with healing times of 4.8 days, 7.0 days, and 14.0 days, respectively. Percentages of cured patients were 70%, 45%, and 7.5%, respectively. In the second study, 60 men were randomized into two groups receiving 0.5% aloe vera extract in a hydrophilic cream base or placebo. The trial had comparable favorable results to the previously discussed trial. Additionally, in vitro testing has demonstrated virucidal effects of anthraquinones and anthraquinone derivatives such as emodin, a component of aloe.

Cat’s Claw

The use of cat’s claw, una de goto, by traditional healers of tropical South America extends back in history for an unknown length of time as part of oral tradition, where it was used to treat gastric ulcers, as an anti-inflammatory, antitumor, and antirheumatic, among other uses ranging from fevers and diarrhea to contraception and female genitourinary cancers. It is also used in the treatment of disharmony between body and spirit, or what we might call anxiety. Inhibition of herpes simplex virus-1 and -2 was demonstrated in vitro by a standardized extract of cat’s claw. H. genitalis was significantly more susceptible to inactivation by the extract than H. labialis. Cat’s claw appears to selectively modulate ovarian hormone function and therefore should be used with care in women with hormonal dysregulation, particularly progesterone insufficiency. It is completely contraindicated in pregnancy. The herb has demonstrated significant in vitro and in vivo immunostimulatory, immunoregulatory, and immunosuppressive, and anti-inflammatory effects, specifically, enhanced lymphocyte production and inhibition of tumor necrosis factor alpha (TNF-a) in a dose-dependent manner. Therefore, it is cautioned any patients on immunomodulating therapies (e.g., immuno-suppressant, hyperimmunoglobulin therapy, receiving vaccinations) avoid the use of cat’s claw and caution be exercised in patients with autoimmune conditions. Use of cat’s claw containing products is entirely contraindicated during pregnancy and lactation; however, it has been used traditionally in the immediate postpartum period for recovery after childbirth, and may facilitate milk supply through estrogen modulation.

Echinacea

Echinacea is a popular herb used to prevent and mitigate viral infections, and also to prevent recurrent infection. It is commonly used as a tincture or decoction as part of a protocol for herpes simplex virus infection. Midwives rely on it in pregnancy as one of the antivirals considered safe to use during that time. In a 5-month uncontrolled clinical study of 4598 patients, a salve prepared from the juice of the aerial portion of Echinacea purpurea was reported to have an 85% success rate in the treatment of a number of inflammatory skin conditions, among them Herpes simplex eruptions. Echinacea is used by herbalists during pregnancy for the prevention of herpes outbreaks. Longitudinal use of echinacea in pregnancy was evaluated for safety and outcomes by Gallo et al. In a prospective study, 206 Canadian women, already taking echinacea-containing products, were compared with a matched cohort not taking echinacea. The products mostly contained E. angustifolia and E. purpurea, although one respondent took E. pallida. Thirty-eight percent took the tincture at a dose of up to 30 drops daily and 58% took tablets or capsules at a dose of 250 to 1000 mg / day. Echinacea use was primarily in the first trimester (54%); 8% used echinacea during all three trimesters. There were no statistical differences between pregnancy outcomes in the two groups nor were there statistically significant differences in the neonates.

Lemon Balm

Lemon balm has classically been used as an uplifting herb for the treatment of stress and anxiety. Rich in volatile oils, in vitro and clinical research conducted over the past decade has demonstrated impressive results using lemon balm ointment as a local therapy in the treatment and prevention of herpes outbreaks. In one study, four different concentrations of volatile oils extracted from lemon balm were examined for the effects against herpes simplex virus-2. At concentrations of 200 μg / mL, replication of herpes simplex virus-2 was inhibited, indicating that the M. officinalis L. extract contains an anti-herpes simplex virus-2 substance. Another study, a double-blind, placebo-controlled, randomized trial, was carried out with the aim of proving efficacy of standardized and highly concentrated lemon balm cream for the therapy of herpes simplex labialis. Sixty-six patients with a history of recurrent herpes labialis (at least four episodes per year) in one center were treated topically; 34 of them with lemon balm cream and 32 with placebo. The cream had to be smeared on the affected area four times daily over 5 days. A combined symptom score of the values for complaints, size of affected area, and blisters at day 2 of therapy was formed as the primary target parameter. A significant difference seen in the combined symptom score on the second day of treatment is of particular importance because symptoms are usually worst at that time. In addition to reducing the duration of the healing period, the treatment led to prevention of spreading of the infection and had a rapid effect on common herpes symptoms including itching, tingling, burning, stabbing, swelling, tautness, and erythema. Some indication exists that the intervals between the periods with herpes might be prolonged with balm mint cream treatment. There is little reason to expect the development of resistance to treatment. Commercial lemon balm extract concentrated creams for topical use are available over the counter and in herbal pharmacies.

Licorice

Numerous in vitro and in vivo studies have shown licorice preparations to have antiviral, antiherpetic, anti-inflammatory, antiulcer, anticarcinogenic, and a wide variety of immunomodulating effects. Licorice root is taken singly or in combination as a tea, tincture, or powdered extract in capsules or tablets. It is also applied topically for local relief of swelling and irritation. The herb is indispensable for its inhibitory effects on the virus, its anti-inflammatory effects to reduce pain and swelling of lesions, and its immunomodulatory effects to enhance host resistance and reduce episodes of active lesions. Glycyrrhizic acid has demonstrated lipoxygenase, cyclooxygenase, and protein kinase C inhibition. Active fractions include triterpenoids like glycyrrhizin and its aglycone glycyrrhizic acid, polyphenols, and immunomodulating heteropolysaccharides. Licorice extract inhibited the growth and cytopathology of herpes, as well as inactivating herpes simplex virus particles irreversibly. In vivo, glycyrrhizin (GR), administered intraperitoneally could increase the survival rate of mice by 2.5 times (37.5%-39.0% to 81.8%-83.3%) that were infected by herpes simplex virus-1 with herpetic encephalitis. GR also reduced herpes simplex virus-1 replication in vivo. Glycyrrhizic acid inhibits the growth of several DNA and RNA viruses in cell cultures and inactivates Herpes simplex 1 virus irreversibly. A recent study shows that treatment of cells latently infected with Kaposi’s sarcoma-associated herpes virus (KSHV), a member of the herpes family, with glycyrrhizic acid, a component of licorice, reduces synthesis of a viral latency protein and induces apoptosis of infected cells, suggesting a novel way to interrupt latency.

Reishi

Considered an adaptogenic and immunomodulating herb, a number of studies have demonstrated activity of Reishi against herpes simplex virus. One study, looking at the mechanisms of action of Reishi against herpes simplex virus-1 and -2 found that the Ganoderma lucidum proteoglycan (GLPG), obtained by liquid fermentation of the mycelia, works by inhibiting viral replication by interfering with the early events of viral adsorption and entry into target cells. Two protein-bound polysaccharides, a neutral protein-bound polysaccharide (NPBP) and an acidic protein-bound polysaccharide (APBP), isolated from water soluble substances of Reishi were also found to be effective against herpes simplex virus-1 and -2. APBP was found to have a direct virucidal effect on herpes simplex virus-1 and -2. APBP did not induce interferon (IFN) or IFN-like materials in vitro and is not expected to induce a change from a normal state to an antiviral state. APBP in concentrations of 100 and 90 ng / mL inhibited up to 50% of the attachment of herpes simplex virus-1 and -2 to cells and was also found to prevent penetration of both types of herpes simplex virus into cells. These results show that the antiherpetic activity of APBP seems to be related to its binding with herpes simplex virus-specific glycoproteins responsible for attachment and penetration, and APBP impedes the complex interactions of viruses with cell plasma membranes. Virucidal effects of Reishi extracts have also been identified by other researchers. A study by Oh et al. demonstrated potent synergistic antiviral effects against herpes simplex virus-1 and -2 showed when combining APBP and acyclovir, suggesting the development of APBP as a new antiherpetic agent. Reishi has also demonstrated beneficial effects in the treatment of herpes zoster, reducing postherpetic neuralgia. Reishi is usually taken as a decoction or tablet. Although tinctures are also available, the polysacchar-ides are likely more bioavailable in whole or water-extracted forms.

Sage and Rhubarb Combination

Essential oil (EO) rich herbs, for example, thyme (Thymus vulgaris), tea tree, and lemon balm, and anthraquinone-rich herbs such as aloe and St. John’s wort all contain antimicrobial activity, some specifically against herpes simplex virus. A combination ointment containing sage and rhubarb extracts, the former essential oil rich and the latter anthraquinone-rich, and a product containing sage alone, were evaluated for their efficacy against herpes simplex virus. A total of 149 patients participated: 145 (111 female, 34 male) of whom 64 received the rhubarb-sage cream, 40 the sage cream, and 41 Zovirax cream. They could be evaluated by intention-to-treat analysis. The dried rhubarb extract used was a standardized aqueous-ethanolic extract according to the German Pharmacopoeia and the dried sage extract an aqueous extract. The reference product was Zovirax cream with the active ingredient acyclovir. The mean time to healing in all cured patients was 7.6 days with the sage cream, 6.7 days with the rhubarb-sage cream, and 6.5 days with Zovirax cream. There were statistically significant differences in the course of the symptoms. For the parameter swelling, at the first follow-up visit there was a significant advantage for Zovirax cream compared with sage cream, and for the parameter pain, at the second follow-up visit there was a significant difference in favor of the rhubarb-sage cream compared to the sage cream. The combined topical sage-rhubarb preparation proved to be as effective as topical acyclovir cream and tended to be more active than the sage cream.

St. John’s Wort

Hypericin and related compounds have been shown to have selective activity against viruses, both in vitro and in vivo, including herpes simplex virus-1 and 2. A prospective double-blind placebo-controlled study of St. John’s wort extract compared with placebo was conducted on 110 patients with herpes genitalis. Patients were given a 90-day treatment protocol of 300 mg tid, and 600 mg tid on the days of herpes outbreaks. Symptoms were significantly and equally reduced compared with placebo, including severity of episodes, size of affected area, and numbers of vesicles. Similar trials conducted by Koytchev et al. and Mannel et al. have yielded similar positive results. Herbalists include St. John’s wort in protocol for both internal and topical use for its positive effects on the nervous system, antiviral activity, and topically in tincture or salve, for its mild vulnerary and anti-inflammatory actions.

Tea Tree

Tea tree oil (TTO) has broad spectrum antimicrobial effects in vitro, and is specifically active against herpes simplex virus. One in vitro study looked at the effects of both tea tree oil and eucalyptus oil (EUO) against herpes simplex virus-1 and -2.S At non-cytotoxic concentrations of tea tree oil, plaque formation was reduced by 98.2% and 93.0% for herpes simplex virus-1 and -2, respectively. Noncytotoxic concentrations of eucalyptus oil reduced virus titers by 57.9% for herpes simplex virus-1 and 75.4% for herpes simplex virus-2. Virus titers were reduced significantly with tea tree oil, whereas eucalyptus oil exhibited distinct but less antiviral activity. In order to determine the mode of antiviral action of both essential oils, either cells were pretreated before viral infection or viruses were incubated with tea tree oil or eucalyptus oil before infection, during adsorption or after penetration into the host cells. Plaque formation was clearly reduced, when herpes simplex virus was pretreated with the essential oils prior to adsorption. These results indicate that tea tree oil and eucalyptus oil affect the virus before or during adsorption, but not after penetration into the host cell. Thus, tea tree oil and eucalyptus oil are capable of exerting a direct antiviral effect on herpes simplex virus. Although the active antiherpes components of Australian tea tree and eucalyptus oil are not yet known, their possible application as antiviral agents in recurrent herpes infection is promising. A clinical trial by Carson et al. focused on the effects of topical application of tea tree oil on recurrent herpes labialis (RHL). Patients age 18 to 70 years (n = 18) with a self-reported history of RHL completed the study. Patients who had antiviral therapy in the previous month, long-term steroid therapy, immunocompromised status, pregnancy, lactation, or known tea tree oil allergy were excluded.

Participants presented as soon as possible after onset of a herpes outbreak and randomly received and applied either 6% tea tree oil in an aqueous gel base or placebo gel five times daily and recorded treatments and any adverse effects in a diary. Subjects were assessed in the clinical daily except Sundays, with swabs collected for culture and PCR evaluation for herpes simplex virus. Visits continued until vesicles were completely healed (re-epithelialized) and PCR was negative for herpes simplex virus DNA on two consecutive days. Investigators were blinded to which patients were using which gels. Parameters measured included re-epithelization time, time to crust formation, duration of detectable virus by lab methods, and virus titer. Although most of the parameters did not reach statistical significance, re-epithelialization time was reduced comparable with other common topical treatments. The authors state that the study size may have been too small to draw complete conclusions, and that the study may have been confounded by the fact that eight of the nine patients in the tea tree oil group began the study in the vesicular stage compared with only six in the placebo group. Nonetheless, they concluded that tea tree oil may be a useful and more affordable acceptable alternative to patients and poses little risk of causing resistance.