Herbal Protection for Acute Viral Infections

Over the last few months, headlines around the world have focused on the Ebola epidemic sweeping West Africa. In early August of this year, the World Health Organization defined the outbreak as a Public Health Event of International Concern. Closer to home, the focus has been on the recent outbreak in the US, with calls for special hospitals equipped to handle Ebola and for specialists to recognize and treat the disease as well as to be trained in monitoring travelers at airports.¹

I’ve recently had numerous inquiries from people who are concerned about Ebola. It’s important to understand that the possibility of an Ebola epidemic in the United States is extremely low.² However, because of increasing concern about the disease, I’m presenting information from my research and guidance as far as what I personally would do if I was inadvertently exposed to the virus, or if I actually contracted the disease. Although I have no factual scientific data on any of these recommendations, based on the etiology of Ebola, I would look to the herbal toolbox I have used for decades as my first line of defense.

The Pathology and Treatment of Ebola

There is no question that Ebola is a serious and often fatal illness. The virus is transmitted through direct contact with bodily fluids, and is only transmissible if the carrier is symptomatic. However, the virus can survive for several hours on dry surfaces such as countertops or doorknobs. Symptoms of Ebola include fever, severe headache, muscle pain, weakness, diarrhea, vomiting, abdominal pain, and unexplained hemorrhage (bleeding or bruising). The symptoms of the disease appear from 2 to 21 days after exposure, with the average 8 to 10 days.

The pathological changes associated with an Ebola infection include endothelial disruption, disseminated intravascular coagulation and multiple organ hemorrhage. The pathogenic mechanisms are diverse and include deficiency of hepatic synthesis of coagulation factors caused by hepatocellular necrosis, cytokine storm, increased permeability by vascular endothelial growth factor, complement activation, and disseminated intravascular coagulation in one or more hemorrhagic fevers.

The effects of viral replication on macrophages and dendritic cells cause the major characteristics of Ebola. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation.

There are still no satisfactory biological explanations to account for the extreme virulence of the lethal hemorrhagic disease caused by Ebola in humans. It’s clear that endothelial cell injury is critical in the progression from disseminated intravascular coagulation to multiple organ dysfunction syndrome and subsequent mortality in Ebola patients.^3,4,5,6  Because 79% of all Ebola patients with any type of hemorrhage die, targeting and preventing the pro-inflammatory and hemorrhagic process of Ebola should be a primary focus of medical intervention.

The immune modulator response includes the production of several proinflammatory cytokines and the activation of numerous transcription factors, including NF-kappaB.  The primary target cells of Ebola are dendritic cells, monocytes, macrophages, and Kupffer cells. Although lymphocytes are not infected, bystander lymphocytic apoptosis occurs even at early stages of the infection. During the course of infection, there is marked depletion of NK cells and CD8 and CD4 T lymphocytes by apoptotic cell death.⁷

No FDA-approved prophylactics or post-exposure treatments exist for Ebola. Current procedures for dealing with suspected or confirmed cases include disrupting virus transmission in the form of quarantine and barrier protection. Drug candidates such as rNAPc2, estrogen receptor modulators, siRNA, interferon (IFN), or neutralizing monoclonal antibodies have shown protection when administered shortly after infection. However, none have demonstrated therapeutic benefit beyond the time window of 2 days post infection.^8,9

Important Biomarkers Relative to Ebola

In studies of blood samples from Ebola victims, researchers found that death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia (whereby a virus enters the bloodstream and gains access to the rest of the body) was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of Soluble CD40L. Soluble CD40L is a platelet-derived mediator that links inflammation, hemostasis and vascular dysfunction.^10,11 Fibrin is closely associated with Ebola virus–infected cells with increased levels of D-dimers and tissue plasminogen activator, and decreased concentrations of activated protein C and platelets.

According to the Centers for Disease Control, pediatric patients who have survived Ebola had higher levels of the chemokine regulated on activation, normal T-cell expressed and had lower levels of plasminogen activator inhibitor (PAI) 1, soluble intracellular adhesion molecule, and soluble vascular cell adhesion molecule than did pediatric patients who died. Adult patients had similar levels of these analytes regardless of outcome.

The urokinase-type plaminogen activator-plasmin system plays an important role in many physiological processes including clot lysis, wound healing, and tissue remodeling. PAI-1 is a serine protein inhibitor that is secreted in response to inflammatory reactions.  Platelet alpha granules contain large amounts of PAI-1, which is released during vascular injury and assists in fibrin clot stability. Also, the upregulation of transforming growth factor -β signaling occurs from Ebola-infected cells.¹

Because low levels of PAI-1 correlate with extreme hemorrhaging and mortality in Ebola patients (specifically in pediatric cases) I theorize that the drug tranexamic acid, a synthetic derivative of the amino acid lysine, would be effective at suppressing Ebola related hemorrhaging. Used to treat bleeding disorders (for example, menorrhagia) tranexamic acid promotes clot stability, has an affinity for five lysine-binding sites of plasminogen, and acts as a noncompetitive inhibitor of plasmin. Tranexamic acid has been shown to reduce the need for a blood transfusion in adult patients undergoing elective surgery.¹³ Tranexamic acid is available in tablet form, absorption is 30 to 50% after oral administration, and bioavailability is not affected by food intake. No serious side effects or drug interactions have been reported.

The Traditional Medical System Perspective

Long before the advent of modern conventional medicine, traditional doctors in the East and Western herbalists from the Vitalist and Eclectic traditions were using plants to help people overcome infectious acute diseases. The constellation of symptoms that the patient presented with were considered to be caused by the entrance of pathogenic influences into the body, and appropriate herbal remedies were administered to alleviate symptoms while addressing underlying constitutional imbalances.

At the opposite end of the spectrum, the focus of modern science is to define the specific cellular and molecular changes that take place in the presence of an infection. Research shows that certain immune modulating compounds are associated with viral infections and the resulting symptoms. For example, the induction of interferons (IFN’s) is associated with host immunity and accounts for some of the host symptoms associated with infections, such as muscle aches and soreness. And studies show that NF-kappaB, another immune modulating compound, stimulates replication of acute viruses and is actually obligatory for viral replication.

The goal of traditional medicine is to target the virus with herbs known to inhibit viral replication, to provide additional immune support with herbs specific to acute infections, and to provide the body with herbs that down-regulate the overactive immune response referred to as the ‘cytokine storm,’ the proinflammatory response that ignites hemorrhaging and other life-threatening events.¹⁴ As well, many herbal compounds are effective at reducing NF-kappaB. ^15,16

My Top Herbal Recommendations for Viral Infections

 

Propolis

A resinous material collected by honeybees from plants, propolis is used by bees to seal their hives, and to prevent diseases within the hive. The natural antimicrobial compounds in propolis make it an excellent infection fighter and healing agent. I recommend propolis for colds, flu, sore throat, sore or infected gums, digestive tract problems including ulcers, and topically for wounds, infections, rashes and sores.

As one of my favorite remedies for easing sore throats, I include propolis as a primary botanical ingredient in my protocol for colds and flus. The antiviral properties of propolis help to fight the virus, and the sticky resin adheres to the mucous membranes in the throat, delivering the antiviral action precisely where the cold and flu viruses take hold and multiply. Propolis has the additional benefit of having mild analgesic and anesthetic properties.

Studies have shown that propolis suppresses the IL-6-induced phosphorylation of signal transducer and STAT3, an essential cytokine-activated transcription factor in Th17 development. Researchers note that the action mechanisms of propolis on Th17 differentiation could be instrumental in controlling disturbed cytokine networks in inflammation, autoimmune diseases, and infections. ¹⁷

Two medical journal articles document the activity of propolis specifically against Staphylococcus aureus, the bacterium that causes dangerous and often deadly surgical infections, blood poisoning, and a type of pneumonia. Five to 10 percent of all patients hospitalized in the United States develop such infections, and S. aureus has become resistant to all but one pharmaceutical antibiotic. In a Chinese study, researchers found that extracts of propolis—specifically, sinapic, isoferulic, and caffeic acids—inhibited the growth of S. aureus.¹⁸ A European study reported that ethanol extracts from propolis had a marked synergistic effect on the anti-staph activity of two antibiotics, streptomycin and cloxacillin, and a moderate effect on several others.¹⁹

Another scientific investigation found that propolis inhibits the activity of several streptococcal bacteria species that cause dental caries. Japanese researchers reported that propolis-fed laboratory fats had far fewer caries than those given a regular diet, finding that propolis protected specifically against Streptococcus mutans and several other strep species. These strep species are closely related to the germ that causes strep throat.²⁰ Ethanolic preparations of propolis have been shown to be active against Staphylococcus aureus (ATCC 25923) and to a lesser extent against Pseudomonas aeruginosa (ATCC 27853).²¹

In yet another study, propolis extract was found to possess pronounced virucidal effect against herpes simplex viruses type 1 and type 2, and to also interfere with virus adsorption.²²

 

Elderberry/Elder Flower (Sambucus Nigra)

The flowers, berries, and inner bark of the elder shrub have been used since antiquity in herbal medicine. The berries are rich in vitamin C and a wide range of important flavonoids, including quercetin and anthocyanins, which are believed to account for the therapeutic effects. The flowers contain flavonoids, such as anthocyanins, carotenoids, essential oil, mucilage, and tannins.

Elderberry extract is used as a tonic to alleviate many cold and flu symptoms including runny nose, cough, sore throat, fever, and muscle pain. Recent research shows that the berry extract increases the IFN-β inducing activity of L. acidophilus in dendritic cells, which suggests antiviral and immune-enhancing activity.²³

Israeli scientists have been at the forefront of researching the benefits of elderberry extract, particularly on flu viruses. Virus cells take over healthy cells by puncturing cell walls with tiny spikes called hemagglutinin. These spikes are coated with an enzyme called neuraminidase, which aids in breaking down cell walls. But compounds in elderberry inhibit the activity of neuraminidase and disarm the spikes by binding to them, which thwarts the virus and prevents it from invading cells.

In one well designed Israeli study, researchers tested a standardized extract of the berry (Sambucol) on 40 people and noted a significant improvement in symptoms of the flu or a complete cure in approximately 90 percent of cases within two to three days, compared to six days for a control group. During the convalescent phase, blood tests showed a higher antibody level to influenza virus in the Sambucol group than in the control group.

“No satisfactory medication to cure influenza type A and B is available. Considering the efficacy of the extract in vitro on all strains of influenza virus tested, the clinical results, its low costs, and absence of side-effects, this preparation could offer a possibility for safe treatment for influenza A and B,” concluded the researchers. ^24,25 Another recent study stated that, “The H1N1 inhibition activities of the elderberry flavonoids compare favorably to the known anti-influenza activities of Oseltamivir (Tamiflu; 0.32 microM) and Amantadine (27 microM).²⁶

Other studies show that elder flowers reduce fever and promote sweating, and a unique protein found in elderberry acts as a messenger regulating immune response.²⁷ Elderberry extract inhibits infectious bronchitis virus at an early point during replication, probably by rendering the virus non-infectious.²⁸

 

Boneset (Eupatorium perfoliatum)

Boneset is native to North America, where it was traditionally used by Native Americans to treat, as its name suggests, “break-bone fever” (Dengue fever). Infusions were also used to treat colds, fever, and pain from arthritis and rheumatism. Boneset attained popularity in about 1800 when a particularly virulent flu, characterized by intense bone pain, swept the East Coast. The plant induces profuse sweating which breaks the fever, which in turn relieves the intense aching pain associated with the flu. Boneset also thins mucus secretions, helping to break up lung congestion.

Boneset was one of the most important remedies used by the Eclectic Physicians for the treatment of colds and flus. Felter wrote this: “Boneset is an admirable remedy to break up a common cold, especially when accompanied by deep-seated, aching pain. In every epidemic of influenza it has been used with great advantage. During the severe pandemic of 1918-19 it was one of the safest and most successful remedies employed and contributed much to the successful management of the disease under Eclectic treatment. By many it came to be used as a prophylactic, persons taking it freely apparently escaping attack.”²⁹

The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In a 2013 study, researchers evaluated the immunomodulatory activities and protective effect of Eupatorium polysaccharide against the highly pathogenic H5N1 subtype influenza virus. They found that Eupatorium polysaccharide has immunomodulatory properties and is a potential prophylactic against H5N1 influenza infection.³⁰ In additional research, the ethanol extract of boneset has shown cytotoxic and antibacterial effects.^31,32

 

Forsythia (Fructus Forsythia)

Forsythia (Lian Qiao) is a Chinese medicinal herb in the category of herbs that Clear Heat and Clean Toxins. In TCM terms, its primary function is to eliminate Wind-Heat or early stage febrile disorders. It is often combined with Lonicera in the classic formula “Yin Qiao San”, which is often used at the first sign of a sore throat in a Wind-Heat disorder, such as at the onset of a cold or flu. It is very effective for eliminating the Heat Toxins associated with sore throats and is also known to protect the heart from Heat in the Lungs that may easily be transferred, leading to insomnia and restlessness.³³

The essential oil of Forsythia has demonstrated inhibitory effects against Staph. Aureus, Diplococcus pneumoniae, Bacillus dysenteriae, alpha-hemolytic Strep., and many other infectious organisms, including several types of influenza.³⁴

 

Honeysuckle (Flos Lonicera)

Honeysuckle (Lonicera), referred to as Jin Yin Hua in Traditional Chinese Medicine, is also used to treat Wind-Heat disorders and is categorized as an herb that Clears Heat and Cleans Toxins. Lonicera possesses diaphoretic properties, and is used to Clear Heat in various stages of febrile disorders. It also has the ability to vent Heat from deeper layers of the body outward. Because Lonicera can address deeper layer Heat, it is not only useful for the sore throat, fever, thirst, and perspiration associated with an external disease, but is also beneficial for internal Heat and Toxins manifesting with high fever, strong thirst, and more severe sore throat.

Lonicera, combined with Forsythia, is the chief botanical agent in the classic formula Yin Qiao San, and is used primarily in the management of early onset febrile disorders. Lonicera is also used for venting of Heat and clearing Toxins in other disorders such as dermatological sores, lesions, and ulcerations, and for internal abscesses or diarrhea and dysentery.^33,35

Lonicera has anti-bacterial, anti-inflammatory, and antiviral actions. It has demonstrated a broad spectrum of inhibitory actions against Staphylococcus aureus, beta-hemolytic streptococcus, and other infectious agents and has shown anti-inflammatory and antipyretic effects in mice and rabbits. Several studies have indicated that Lonicera can prevent or shorten the duration of colds and flus.^36,37,38  In addition, Lonicera improves sepsis-induced mortality, enhances bacterial clearance, and attenuates multiple organ failure.³⁹

 

Yarrow (Achillea millefolium)

Yarrow is a common, prolific, and humble herb that possesses immense and diverse healing value. Traditional healers have long recognized the numerous pharmacological properties of yarrow, which include anti-inflammatory, antispasmodic, cytotoxic, antioxidant, antibacterial, antiviral, antiplatelet aggregation, and hemostatic actions.⁴⁰

Yarrow is a classic diaphoretic, and is traditionally combined with boneset, elderflower, and peppermint for easing the fever that accompanies flus. It diffuses and channels heat by inducing perspiration, an essential process for quickly overcoming fever. In addition, the anti-inflammatory and antiviral properties of yarrow help to fight viruses. I theorize that the hemostatic properties of yarrow would also be beneficial in the case of Ebola for helping to check internal bleeding.

Recent studies show that yarrow extract possesses antiviral activity against Newcastle disease, which is a deadly viral disease in the poultry industry.⁴¹ Yarrow extract has also been shown to exert potent anti-rotaviral activity (a common cause of gastroenteritis) after viral adsorption.⁴²

 

Dragon’s blood (Croton lechleri)

Also is known as “sangre de grado” (Spanish for “blood of the dragon”), dragon’s blood has been used in traditional herbal medicine both internally and externally to stop bleeding, heal wounds, and for treating intestinal problems. In Peruvian herbal medicine, dragon’s blood is used internally for hemorrhaging, mouth ulcers, tonsillitis, throat infections, tuberculosis, peptic ulcers, intestinal disorders, rheumatism and to enhance fertility. In Brazilian traditional medicine the sap is used for wounds, hemorrhaging, mouth ulcers and as a general tonic. ⁴³

The results of in vitro and in vivo studies largely support the majority of ethnomedical uses of dragon’s blood. Taspine, a component of dragon’s blood, has been documented to have anti-inflammatory and wound-healing actions. Both taspine and a proanthocyanidin component have also been shown to have antiviral activities. Dragon’s blood has been shown to be effective for stomach ulcers, ulcerative colitis, and Crohn’s disease when taken internally, and is perhaps the most effective agent for infectious diarrhea. ⁴⁴

In addition to taspine, dragon’s blood contains a number of other beneficial phytochemicals, including phenolic compounds, proanthocyanadins and diterpenes, which demonstrate potent anti-bacterial activity as well as wound healing properties.

Today, preparations made from dragon’s blood are found in several pharmaceutical products. A patent describing use of the proanthocyanidin polymer from croton species (SP-303) as an antidiarrheal was issued to Shaman Pharmaceuticals, Inc. USA. A clinical trial of the principal ingredient (SP-303) in patients with HIV-associated diarrhea demonstrated beneficial effects. ^44-48

Controlling The Inflammatory Cascade

It is essential to provide herbal support during an infection to buffer the many cellular pathways that are altered during both acute and chronic inflammation.

Andrographis extract (50% andrographolide)

Andrographolide (AG) is isolated from the plant of Andrographis paniculata and used in traditional medicine for treating viral infection, diarrhea, dysentery and fever.

In two parallel group clinical studies, using Andrographis paniculata (as a fixed proprietary preparation known as Kan Jang) versus amantidine in patients with influenza showed increased recovery and reduced post-influenza complications. Several studies evaluating andrographis and the common cold demonstrated improvement within two to four days of treatment. The immune stimulating properties of andrographis appear to be derived from antibody activity and phagocytosis by macrophages.^57,58,59,60

Nuclear DNA-binding protein high-mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions, such as septic shock, upregulating pro-inflammatory cytokines. Andrographolide is a therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.⁶¹

Melatonin has been shown to target many of the alterations associated with Ebola. Numerous similarities between Ebola virus infection and septic shock have been recognized for more than a decade. Melatonin has been successfully employed for the treatment of sepsis in many experimental and clinical studies. Based on these factors, as the treatments currently available are limited and the useable products are not abundant, melatonin is a safe and readily available adjunct therapy. Additionally, melatonin has a high safety profile and can be orally self-administered; thus, the use of melatonin is compatible with the large scale of this serious outbreak.⁶² Dosage 1-5 mg. taken once per day in evening between 9 and 10 PM.

Red Yeast Rice is an appropriate addition to a protocol for combatting Ebola. Research shows treating the cells with an HMG CoA reductase such as red yeast rice reduces filovirus replication.⁶²

Hemostatic Remedies

1) Yunnan Baiyao TCM formula: internally 2 caps 3-4x daily.

2) Cold water or infusion of yarrow and/or cinnamon (diaphoretic effects as well).

3) Tranexemic acid (drug) inhibits blood clot breakdown and reduces bleeding.

Even though Ebola has been around for more than a decade, the medical world is still in uncharted territory with regards to effective treatment and prevention. Although there is a lack of sufficient research regarding Ebola and effective treatments, I believe that botanical medicine has a great deal to offer in terms of fortifying the body against infection, alleviating symptoms, and helping the immune system overcome acute viral attacks. My hope is that these recommendations will offer guidance and reassurance in dealing with this terrible disease and other pathogens of this nature.

References

• Boulton J. Ebola: where did it come from and where might it go? Br J Nurs. 2014 Oct 9;23(18):988-91. doi: 10.12968/bjon.2014.23.18.988.
• Stephenson J. CDC: Ebola risk to US patients is low, but clinicians should be on alert. 2014 Aug 20;312(7):686. doi: 10.1001/jama.2014.10528
• Takada A1, Kawaoka Y. The pathogenesis of Ebola hemorrhagic fever, Trends Microbiol. 2001 Oct;9(10):506-11.
• Lin SM1, Wang YM, Lin HC, Lee KY, Huang CD, Liu CY, Wang CH, Kuo HP. Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis, Crit Care Med. 2008 Mar;36(3):683-9. doi: 10.1097/CCM.0B013E31816537D8.
• Ansari AA. Clinical features and pathobiology of Ebolavirus infection, J Autoimmun. 2014 Sep 23. pii: S0896-8411(14)00130-9. doi: 10.1016/j.jaut.2014.09.001.
• Bray M1, Geisbert TW. Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever, Int J Biochem Cell Biol. 2005 Aug;37(8):1560-6. Epub 2005 Mar 7.
• Martinez O1, Valmas C, Basler CF. Ebola virus-like particle-induced activation of NF-kappaB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain, 2007 Aug 1;364(2):342-54. Epub 2007 Apr 16.
• Lisa Oestereich^{a, b}, Anja Lüdtke^{a, c}, Stephanie Wurr^{a, b}, Toni Rieger^{a, b}, César Muñoz-Fontela^{a, c}, Stephan Günther, Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model, Antiviral Research Volume 105, May 2014, Pages 17–21
• Wong G1, Qiu X2, Olinger GG3, Kobinger GP Post-exposure therapy of filovirus infections. Trends Microbiol. 2014 Aug;22(8):456-63. doi: 10.1016/j.tim.2014.04.002. Epub 2014 Apr 30.
• McElroy AK , Erickson BR , Flietstra TD , Rollin PE , Nichol ST , Towner JS , Spiropoulou CF . Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome, J Infect Dis. 2014 Aug 15;210(4):558-66. doi: 10.1093/infdis/jiu088. Epub 2014 Feb 12.
• Slobodan Paessler and David H. Walker, Pathogenesis of the Viral Hemorrhagic Fevers Annual Review of Pathology: Mechanisms of Disease 8: 411-440 (Volume publication date January 2013) First published online as a Review in Advance on November 1, 2012 DOI: 10.1146/annurev-pathol-020712-164041
• Kindrachuk J, Wahl-Jensen V, Safronetz D, Trost B, Hoenen T, Arsenault R, Feldmann F, Traynor D, Postnikova E, Kusalik A, Napper S, Blaney JE, Feldmann H, Jahrling PB. Ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes. J Virol. 2014 Sep 1;88(17):9877-92.
• Perel P, Ker K, Morales Uribe CH, Roberts I. Tranexamic acid for reducing mortality in emergency and urgent surgery. Cochrane Database Syst Rev. 2013 Jan 31;1:CD010245. doi: 10.1002/14651858.CD010245.pub2.
• Hensley LE1, Young HA, Jahrling PB, Geisbert TW. Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily, Immunol Lett. 2002 Mar 1;80(3):169-79.
• Nimmerjahn F, Dudziak D, Dirmeier U, Hobom G, Riedel A,Schlee M, et al. Active NF-kappaB signalling is a prerequisite for influenza virus infection. J Gen Virol. 2004;/85:/2347_/
• Wurzer WJ, Ehrhardt C, Pleschka S, Berberich-Siebelt F, Wolff T, Walczak H, et al. NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J Biol Chem. 2004;/279:/30931_/7
• de Figueiredo SM, Nogueira-Machado JA, M Almeida BD, Abreu SR, de Abreu JA, Filho SA, Binda NS, Caligiorne RB. Immunomodulatory Properties of Green Propolis. Recent Pat Endocr Metab Immune Drug Discov. 2014 Jun 19
• Qiao Z, China Journal of Chinese Materi Medica, Aug. 1991;16:481-2
• Krol W, Arzneimittel-Forschung, May 1993;43:607-9
• Ikeno K, Caries research, 1991;25:347-51
• Massaro CF, Katouli M, Grkovic T, Vu H, Quinn RJ, Heard TA, Carvalho C, Manley-Harris M, Wallace HM, Brooks P. Anti-staphylococcal activity of C-methyl flavanones from propolis of Australian stingless bees (Tetragonula carbonaria) and fruit resins of Corymbia torelliana (Myrtaceae). 2014 Jun;95:247-57. doi: 10.1016/j.fitote.2014.03.024. Epub 2014 Apr 4.
• Bankova V, Galabov AS, Antonova D, Vilhelmova N, Di Perri B. Chemical composition of Propolis Extract ACF® and activity against herpes simplex virus. 2014 Sep 25;21(11):1432-8. doi: 10.1016/j.phymed.2014.04.026. Epub 2014 Jul 8.
• Frøkiær H1, Henningsen L, Metzdorff SB, Weiss G, Roller M, Flanagan J, Fromentin E, Ibarra A. Astragalus root and elderberry fruit extracts enhance the IFN-β stimulatory effects of Lactobacillus acidophilus in murine-derived dendritic cells. PLoS One. 2012;7(10):e47878. doi: 10.1371/journal.pone.0047878. Epub 2012 Oct 30.
• Zakay-Rones Z, Varsarno N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra) during an outbreak of influenza B Panama. Journal of Alternative Complementary Medicine 1995; 1:361-9
• Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, Mumcuoglu M. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med. 1995 Winter;1(4):361-9.
• Roschek B Jr, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. 2009 Jul;70(10):1255-61. Epub 2009 Aug 12.
• Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines. Eur Cytokine Netw. 2001 Apr-Jun;12(2):290-6.
• Chen C, Zuckerman DM, Brantley S, Sharpe M, Childress K, Hoiczyk E, Pendleton AR. Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC Vet Res. 2014 Jan 16;10:24. doi: 10.1186/1746-6148-10-24.
• Felter, M.D., Harvey Wickes, The Eclectic Materia Medica, Pharmacology and Therapeutics, pg. 171-172, 1922, Cincinnati, OH
• Jin Y, Zhang Y, Wan C, Wang H, Hou L, Chang J, Fan K, Xie X. Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection. Evid Based Complement Alternat Med. 2013;2013:194976. doi: 10.1155/2013/194976. Epub 2013 Sep 18.
• Gupta M, Mazumder UK, Chaudhuri I, Chaudhuri RK, Bose P, Bhattacharya S, Manikandan L, Patra S. Antimicrobial activity of Eupatorium ayapana.Fitoterapia. 2002 Apr;73(2):168-70
• Habtemariam S, Macpherson AM. Cytotoxicity and antibacterial activity of ethanol extract from leaves of a herbal drug, boneset (Eupatorium perfoliatum). Phytother Res. 2000 Nov;14(7):575-7.
• Zhong Yao Xue (Chinese Herbology), 1998;169:171
• Xin Yi Xue (New Medicine), 1975; 6(3):155
• Ke Yan Tong Xun (Journal of Science and Research), 1982 (3):35
• Jiang Xi Xin Yi Yao (Jiangxi New Medicine and Herbology); 1960; (1):34
• Guang Dong Zhong Yi (Guang Dong Chinese Medicine), 1962 5:25
• Shang Hai Zhong Yi Yao Za Zhi, Shanghai Journal of Chinese Medicine and Herbology, 1983; 9:27
• Kim SJ, Yoon SJ, Kim YM, Hong SW, Yeon SH, Choe KI, Lee SM. HS-23, Lonicera japonica extract, attenuates septic injury by suppressing toll-like receptor 4 signaling. J Ethnopharmacol. 2014 Aug 8;155(1):256-66. doi: 10.1016/j.jep.2014.05.021. Epub 2014 May 24.
• Moradkhani S, Kobarfard F, Ayatollahi SA. Phytochemical Investigations on Chemical Constituents of Achillea tenuifolia Lam. Iran J Pharm Res. 2014 Summer;13(3):1049-54.
• Rezatofighi SE, Seydabadi A, Seyyed Nejad SM. Evaluating the Efficacy of Achillea millefolium and Thymus vulgaris Extracts Against Newcastle Disease Virus in Ovo. Jundishapur J Microbiol. 2014 Feb;7(2):e9016. doi: 10.5812/jjm.9016. Epub 2014 Feb 1.
• Taherkhani R, Farshadpour F, Makvandi M. In Vitro Anti-rotaviral Activity of Achillea kellalensis, Jundishapur J Nat Pharm Prod. 2013 Aug;8(3):138-43. Epub 2013 Jul 17.
• Wolters Kluwer Health, Inc. Dragon’s Blood. Review of Natural Products. Facts and comparisons4.0 [online]. 2004.
• Jones K. Review of sangre de drago (Croton lechleri)–a South American tree sap in the treatment of diarrhea, inflammation, insect bites, viral infections, and wounds: traditional uses to clinical research. J Altern Complement Med. 2003 Dec;9(6):877-96. Review.
• Chordia P, MacArthur RD. Crofelemer, a novel agent for treatment of non-infectious diarrhea in HIV-infected persons. Expert Rev Gastroenterol Hepatol. 2013 Sep;7(7):591-600. doi: 10.1586/17474124.2013.832493. Review.
• Frampton JE. Crofelemer: a review of its use in the management of non-infectious diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy. 2013 Jul;73(10):1121-9. doi: 10.1007/s40265-013-0083-6. Review.
• Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels.
• Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. Cottreau J, Tucker A, Crutchley R, Garey KW. Crofelemer for the treatment of secretory diarrhea. Expert Rev Gastroenterol Hepatol. 2012 Feb;6(1):17-23. doi: 10.1586/egh.11.87. Review.
• Kulichenko, L. Kireyeva and E. Malyshikina et al., A randomized, controlled study of Kan Jang versus amantidine in the treatment of influenza in Volgograd, J Herb Pharmacother 3 (2003), pp. 77–93.
• Poolsup, C. Suthisisang and S. Prathanturanrug et al., Andrographis in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials, J Clin Pharm Ther 29 (2004), pp. 37–45.
• Melchoir, A.A. Spasov and O.V. Ostrovskij et al., Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan Jang) in the treatment of uncomplicated upper-respiratory tract infection, Phytomedicine 7 (2000), pp. 341–350.
• Puri, R. Saxena and R.P. Saxena et al., Immunostimulant agents from Andrographis paniculata, J Nat Prod 56 (1993), pp. 995–999.
• Lee W, Ku S, Yoo H, Song K, Bae J. Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis. Acta Physiol (Oxf). 2014 May;211(1):176-87. doi: 10.1111/apha.12264. Epub 2014 Mar 24.
• Tan DX , Korkmaz A, Reiter RJ, Manchester LC. Ebola virus disease: potential use of melatonin as a treatment. J Pineal Res. 2014 Sep 27. doi: 10.1111/jpi.12186.
• Salvatore Patanè, Ebola: Is there a hope from treatment with cardiovascular drugs? International Journal of Cardiology Available online 26 August 2014, DOI: 10.1016/j.ijcard.2014.08.114