Hyssopus officinalis / Hyssop

Hyssop Flora Batava
The use of hyssop as an herbal remedy dates back to Biblical times. It is mentioned in both the Old and New Testaments as a cleansing agent (although these references may be to other species of hyssop such as Origanum aegypticum or to Origanum syriacum, rather than Hyssopus officinalis) (1;​2).
Hyssop has been prescribed for a multitude of medical conditions. It has been traditionally used as an antispasmodic, expectorant, emmenagogue, stimulant, carminative, peripheral vasodilator, anti-inflammatory, anticatarrhal, antispasmodic, tonic and sweat-inducer. However, both the alcoholic extract and decoction have been used to inhibit sweating (3). Hyssop is used specifically for cough, bronchitis and chronic catarrhal, and also for its tonic effects on the digestive, urinary, nervous and bronchial systems (1;​4). Hot hyssop decoction vapors have also been used to treat inflammation and tinnitus (5).

Historical or Theoretical Uses which Lack Sufficient Evidence:
Abscess (peritonsillar), anemia, antifungal, anthelminthic, anti-inflammatory, antioxidant, antispasmodic, antitussive, antiviral, anxiety, asthma, bronchitis, bruises, burns, calming, cancer, cardiovascular conditions, carminative, catarrh, chronic venous insufficiency (CVI), circulatory disorders, common cold, cosmetic, cough, depression, diabetes mellitus type 1, diaphoretic, digestive tonic, diuretic, dyspepsia, emmenagogue, epilepsy, exhaustion, expectorant, fever, food flavoring, flu, gallbladder disorders, gout, herpes simplex, HIV (6;​7), hyperlipidemia, hysteria, influenza, intestinal inflammation, intestinal worms, Kaposi's sarcoma, leukemia, liver conditions, melanoma, nephritis, night sweats, ophthalmia, perfume, peripheral vasodilator, pleurisy, poor circulation, respiratory infections, rheumatism, rhinitis, respiratory congestion, sedative, seizure (petit mal), sore throat, stimulant, stress, tinnitus, tonic, tonsillitis, toothache, vulnerary.

Expert Opinion and Historic/Folkloric Precedent:
Hyssop is a name of Greek origin. Many of the most well-known doctors of history have recommended hyssop to their patients. Hippocrates prescribed it for pleurisy, while Dioscorides prescribed hyssop for asthma and phlegm. Hyssopos of Dioscorides was named from azob (a holy herb), because it was used for cleaning sacred places; traditionally it has been used as a strewing herb.

Brief Safety Summary:
Possibly unsafe: When used by children or by women that are pregnant or breast feeding due to lack of available evidence When used by patients on antiviral medications (6;​7), immunosuppressants, or glucocorticoids (8).
Likely unsafe: When used in patients with epilepsy, fever, and hypertension (9;​10). When used by patients with decreased seizure thresholds (9;​10). When adults consume more than 10 to 30 drops daily of hyssop oil or children consume 2 to 3 drops daily of hyssop oil (9;​10).

Dosing/Toxicology
General:
Recommended doses are based on those most commonly used in available trials, or on historical practice. However, with natural products it is often not clear what the optimal doses are to balance efficacy and safety. Preparation of products may vary from manufacturer to manufacturer, and from batch to batch within one manufacturer. Because it is often not clear what the active component(s) of a product is, standardization may not be possible, and the clinical effects of different brands may not be comparable.

Dosing:
Adult (age ≥18):
Oral:
General: 2g of dried herb infused in boiling water three times daily has been given, theoretically.
Children (age <18):Insufficient available evidence.

Toxicology:
Several cases of toxicity resulting from ingestion of hyssop's essential oil have been reported (9;​10). The clinical symptoms of hyssop toxicity include convulsive seizures that resemble epileptic fits and vomiting, and may develop within a few minutes to two hours. The commercially available essential oil of hyssop contains pinocamphone and isopinocamphone, which may be responsible for the neurotoxicity; injections of relatively low dosages of these drugs (0.02mL/kg) proved to be lethal in rats (10).

Mechanism of Action
Pharmacology:

Constituents: Several chemical constituents of hyssop have been identified, including pinocamphone, pinene, borneol, geraniol, thujone, camphene, limonene and phellandrene. Terpenoids with known pharmacological actions that are found in hyssop include marrubiin, ursolic acid and oleanolic acid. Other characteristic compounds identified in hyssop are hyssopin (a glucoside), caffeic acid, tannins and resin. The volatile oil of hyssop is composed of camphor, pinacaphone, thujone, isopinocamphone, alpha- and beta-pinene, alpha terpinene, linalool, and bornylacetate.

Anti-hyperlipidemia effects: From extensive in vitro and in vivo studies, both oleanolic acid and ursolic acid have recognized anti-hyperlipidemic properties (13).

Anti-inflammatory effects: From extensive in vitro and in vivo studies, both oleanolic acid and ursolic acid have recognized anti-inflammatory properties (13).

Anti-proliferative effects: Ursolic acid, a constituent of hyssop, was found to induce apoptosis in human leukemia cells. This effect may have been a result of enhanced intracellular Ca2+ levels, since lowering the intracellular Ca2+ level by different agents inhibits the apoptotic action of ursolic acid (14). The antiproliferative action of ursolic acid was also indicated in a mouse melanoma cell line (15).

Antiviral effects: Crude extracts of dried leaves of Hyssop officinalis have shown strong anti-HIV activity as measured by inhibition of syncytia formation, HIV reverse transcriptase (RT), and p17 and p24 antigen expression; however, these extracts were non-toxic to the uninfected Molt-3 cells (6). Ether extracts from direct extraction (Procedure I), after removal of tannins (Procedure II), or from the residue after dialysis of the crude extract (Procedure III), showed good antiviral activity. Methanol extracts, subsequent to ether, chloroform and chloroform ethanol extractions, derived from procedure I or II, but not III, also showed very strong anti-HIV activity. In addition, the residual material after methanol extractions still showed strong activity. Caffeic acid was identified in the ether extract of procedure I by HPLC and UV spectroscopy. Hyssop officinalis extracts contain caffeic acid, unidentified tannins, and possibly a third class of unidentified higher molecular weight compounds that exhibit strong anti-HIV activity, and may be useful in the treatment of patients with AIDS.
Gollapudi, et al. isolated a polysaccharide (MAR-10) from the aqueous extract of the Hyssop officinalis and examined for its activity against HIV-1 (SF strain) in HUT78 T cell line and primary cultures of peripheral blood mononuclear cells (7). MAR-10, in a concentration-dependent manner, inhibited HIV-1 replication as demonstrated by the inhibition of HIV-1 p24 antigen and syncytia formation. Furthermore, MAR-10 had no significant direct toxicity or effect on lymphocyte functions or CD4+ and CD8+ T cell counts. In addition, MAR-10 has broad spectrum anti-glycosidase activity.

Cardiovascular effects: According to a clinical trial, flavonoids found in hyssop, including diosmin and hesperidin, may slightly improve chronic venous insufficiency (CVI) (16).

Diabetes mellitus type 1 effects: Daflon® 500 (a mixture of diosmin [90%] and hesperidin [10%]) proved to be effective in decreasing glycation in type I diabetic patients (11;​12).

Expectorant effects: Marrubiin, a bitter diterpenoid found in hyssop, irritates the lining of the throat, causing an expectorant action (2).
Gall bladder effects: Marrubiin, found in hyssop, is a bitter diterpenoid that increases the production of bile in laboratory animals (2).

References
  1. Brown, D. Encyclopedia of Herbs and Their Uses. 1995.
  2. Tyler VE. Herbs of Choice: The Therapeutic Use of Phytomedicinals.
  3. Varga, E., Hajdu, Z., Veres, K., Mathe, I., Nemeth, E., Pluhar, Z., and Bernath, J. [Investigation of variation of the production of biological and chemical compounds of Hyssopus officinalis L.]. Acta Pharm Hung. 1998;68(3):183-188. View Abstract
  4. Hoffmann D. Therapeutic herbalism. A correspondence course in phytotherapy. 1995;4:64-65.
  5. Culpepper. Culpeper's Complete Herbal. 1995;129.
  6. Kreis, W., Kaplan, M. H., Freeman, J., Sun, D. K., and Sarin, P. S. Inhibition of HIV replication by Hyssop officinalis extracts. Antiviral Res. 1990;14(6):323-337. View Abstract
  7. Gollapudi, S., Sharma, H. A., Aggarwal, S., Byers, L. D., Ensley, H. E., and Gupta, S. Isolation of a previously unidentified polysaccharide (MAR-10) from Hyssop officinalis that exhibits strong activity against human immunodeficiency virus type 1. Biochem.Biophys.Res.Commun. 5-5-1995;210(1):145-151. View Abstract
  8. Deng, Y. Y., Chen, Y. P., Wang, L., Hu, Z., Jin, Y., Shen, L., Zhu, R., and Zhong, Y. [Clinical study on treatment of mid-advanced crescentic nephritis by qingre huoxue recipe]. Zhongguo Zhong.Xi.Yi.Jie.He.Za Zhi. 2004;24(12):1084-1086. View Abstract
  9. Burkhard, P. R., Burkhardt, K., Haenggeli, C. A., and Landis, T. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246(8):667-670. View Abstract
  10. Millet, Y., Jouglard, J., Steinmetz, M. D., Tognetti, P., Joanny, P., and Arditti, J. Toxicity of some essential plant oils. Clinical and experimental study. Clin Toxicol. 1981;18(12):1485-1498. View Abstract
  11. Keenoy, B., Vertommen, J., and De, Leeuw, I. The effect of flavonoid treatment on the glycation and antioxidant status in Type 1 diabetic patients. Diabetes Nutr Metab 1999;12(4):256-263. View Abstract
  12. Jantet, G. RELIEF study: first consolidated European data. Reflux assEssment and quaLity of lIfe improvement with micronized Flavonoids. Angiology 2000;51(1):31-37. View Abstract
  13. Jie, L. Pharmacology of oleanolic acid and ursolic acid. Journal of Ethnopharmacology 1-2-1995;49(2-1):57-68.
  14. Baek, J. H., Lee, Y. S., Kang, C. M., Kim, J. A., Kwon, K. S., Son, H. C., and Kim, K. W. Intracellular Ca2+ release mediates ursolic acid-induced apoptosis in human leukemic HL-60 cells. Int J Cancer 11-27-1997;73(5):725-728. View Abstract
  15. Es-saady, D., Simon, A., Ollier, M., Maurizis, J. C., Chulia, A. J., and Delage, C. Inhibitory effect of ursolic acid on B16 proliferation through cell cycle arrest. Cancer Lett. 9-10-1996;106(2):193-197. View Abstract
  16. Cesarone, M. R., Belcaro, G., Pellegrini, L., Ledda, A., Di Renzo, A., Vinciguerra, G., Ricci, A., Gizzi, G., Ippolito, E., Fano, F., Dugall, M., Acerbi, G., and Cacchio, M. HR, 0-(beta-hydroxyethyl)-rutosides, in comparison with diosmin+hesperidin in chronic venous insufficiency and venous microangiopathy: an independent, prospective, comparative registry study. Angiology 2005;56(1):1-8. View Abstract
Monografie NatStandard/Hyssop.



Antiviral Res. 1990 Dec;14(6):323-37. Inhibition of HIV replication by Hyssop officinalis extracts.
Kreis W1, Kaplan MH, Freeman J, Sun DK, Sarin PS.
Crude extracts of dried leaves of Hyssop officinalis showed strong anti-HIV activity as measured by inhibition of syncytia formation, HIV reverse transcriptase (RT), and p17 and p24 antigen expression, but were non-toxic to the uninfected Molt-3 cells. Ether extracts from direct extraction (Procedure I), after removal of tannins (Procedure II), or from the residue after dialysis of the crude extract (Procedure III), showed good antiviral activity. Methanol extracts, subsequent to ether, chloroform and chloroform ethanol extractions, derived from procedure I or II, but not III, also showed very strong anti-HIV activity. In addition, the residual material after methanol extractions still showed strong activity. Caffeic acid was identified in the ether extract of procedure I by HPLC and UV spectroscopy. Commercial caffeic acid showed good antiviral activity in the RT assay and high to moderate activity in the syncytia assay and the p17 and p24 antigen expression. Tannic acid and gallic acid, common to other teas, could not be identified in our extracts. When commercial products of these two acids were tested in our assay systems, they showed high to moderate activity against HIV-1. Hyssop officinalis extracts contain caffeic acid, unidentified tannins, and possibly a third class of unidentified higher molecular weight compounds that exhibit strong anti-HIV activity, and may be useful in the treatment of patients with AIDS.


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