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Pulmonary administration of Artemisia afra against tuberculosis

April 29, 2016 - 09:34 -- Pierre Lutgen

Many constituents of medicinal herbs have a low bioavailabity, especially if administered orally. They do not pass the intestinal barrier. This is particularly the case for essential oils. A study (Ryuichi Fujisaki et al., of the in vitro and in vivo antiplasmodial activity of 47 essential oils showed that several have strong in vitro antiplasmodial activities, with IC50 values < 1.0 µg/ml. But notably these oils showed no efficacy when administered orally.

Pulmonary administration of drugs is often desirable for pulmonary diseases and it can also be a good route for systemic drug administration. It can be done in the form of particles , but the particle size needs to be < 5 µm. The delivery of active compounds directly to the lungs provides a local treatment and effectively delivers the drug to the site of action. In this way, smaller doses are able to achieve a maximal therapeutic effect and have less risk of side-effects. The rapid and efficient absorption of drugs in the lungs is facilitated by the large surface area, high blood perfusion with abundancy of capillaries and the thin air-blood barrier. A breath holding pause after inhalation of the aerosols favours gravity settlement of a larger proportion of particles which would otherwise remain airborne during expiration (D Pavia et al., Thorax, 1977, 32, 194-197).

Several Japanese studies show that the inhalation of monoterpenes like α-pinene, limonene ot 1,8-cineole boost the immune system. In a paper titled „A day trip to a forest park“ (Li Q w et al., J Biol Regul Homeost Agents, 2010, 24, 157-65) the authors show that a 2-night/3-day trips to forest parks enhanced human NK activity, the number of NK cells and that the effect lasted for more than 7 days after the trip in both male and female subjects. Similar effects were noticed for single day trips. Essential oils were found in the smoke of “tira-capeta”, a herbal cigarette used by some quilombolas living in pantanal wetlands of Brazil (G Negri et al., Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 2010, 20(3): 310-316).

The lungs have received attention as a portal for drug delivery in tuberculosis (TB) from researchers addressing diverse objectives. (A Misra et al., Tuberculosis 2011 911:71-81). Artemisia afra is often used in steam inhalation. A study in South Africa (Sizwe Joel Mjikiza et al., J of Ethnopharmacol, 2013, 149, 648-655) tried to determine the effects of Artemisia afra steam inhalation, nebulized luteolin and nebulized aqueous leaf extract on lung function. Artemisia afra extract contained significantly higher luteolin levels than the crude dried leaves. Nebulized Artemisia afra extract produced the greatest improvements. Nebulisation with Artemisia afra extract yielded higher quantities of absorbed luteolin than luteolin nebulization. In a survey made in the Limpopo province the most regularly used plant species to treat TB was Artemisia afra (SS Semenya et al., Afr J Trad Complement Med. 2013, 10, 316-323). The leaves of the plant are crushed, wrapped in newspaper and smoked twice a day, or leaves are burned in a hut and smoke inhaled twice a day. All this confirms the efficacy of Artemisia afra phytotherapy in experimental tuberculosis as described by S Ntutela (Tuberculosis , 2009 89: S33–S40). A more recent paper shows that luteolin inhibits the pathogenesis and progression of tuberculosis (K Mayer-Barber et al, Nature, June 2014).

Pulmonary vaccination is a promising route for immunization against tuberculosis because the lung is the natural site of infection with Mycobacterium tuberculosis (J Todoroff et al., PloS ONE 2013, e63344). By this approach high levels of drug are concentrated at the site of action in the lung. Inulin is often used as adjuvant for stabilization (MA Mensink et al., Carbohydrate Polymers, 2015, 134, 418-428).

In traditional healing, the burning of selected indigenous medicinal plants and the inhalation of the liberated smoke are widely accepted and a practical route of administration. A study from South Africa elucidated the rationale behind this commonly practiced treatment by examining the antimicrobial activity of five indigenous South African plants, including Artemisia afra, commonly administered through inhalation. The result of the bioassay suggests that the combustion process produces an « extract » with superior antimicrobial activity and lower MIC than methanol or acetone extracts (M Braithwaite et al., J Ethnopharmacol 2008, 119-3, 501-506).

Terpenes contribute to the percutaneous permeation enhancement of drugs. Terpenes from natural sources are generally considered to be less toxic than synthetic chemicals and lower irritation potential compared to surfactants. Many of these terpenes are considered as safe agents by US FDA. Limonene for example is considered as essential for increasing the penetration of poorly permeable drugs (Bharti Sapra et al., The AAPS Journal, 10-1, 2008, 120-126).

A technique to increase the bioavailability of drugs which are with little effect in oral administration is moxibustion, which has been applied in treating a great range of diseases. (Hongyong Deng et al., Evid Based Complement and Alternat Medic, 2013, Article ID 379291). Moxa is shredded Artemisia that is burned on or near the body to produce local healing, imparting borneol, 1,8-cineole, other terpenes or constituents to the body. The herb Artemisia vulgaris (called argyii in China), also known as Chinese mugwort was recorded as an internal medicine by the Taoist herbalist Tao Hongjing around 500 A.D (Ming Yi Bie Lu).

Pierre Lutgen


Submitted by Pierre Lutgen on

Several authors have documented the efficacy of luteolin against pulmonary diseases. The highest concentration of luteolin is found in Artemisia afra at 1.9 mg/g. In Artemisia absinthium 0.7 mg/g are found. A few studies show only traces of luteolin in Artemisia annua

     A. Dube, Thesis, Artemisia afra, University Western Cape, 2006.

Mucus overproductionis one of the most important pathological features of chronic inflammatory airway diseases that contribute to morbidity and mortality. It reduces ciliar motility, damages local defensive functions and promotes bacterial colonization. As a natural flavonoid luteolin has multiple biological activities, such as anti-inflammatory and anti-oxidant properties. A Chinese study found that the administration of luteolin effectively attenuates mucus overproduction.

    Mei-Li Shen, Chen-Hung, Luteolin attenuates airway mucus overproduction. Scientific Reports, 2016, 6 : 32576

    Kuo My, Liao MF, Luteolin attenuates the pulmonary inflammatory response. Food and Chemical Toxicology, 2011, 49(10) : 2660-6

    M. Das, A Ram, Luteolin alleviates Bronchonstriction and Airway Hyperreactivity, Inflamm Res, 2003, 52,(3): 101-6

    Haiyan Yan, LinlinMa, Luteolin decreases the yield of Influenza A virus. J Nat Med. 2019, 73, 487-496

Strong support comes from a very recent study. The flavone luteolin has been shown to have broad antiviral properties. Luteolin specifically binds to surface spike protein of SARS-Cov-2 and inhibits entry of the virus into host cells. Moreover, luteolin has anti-inflammatory properties and inhibits mast cells which invade the lungs when triggered by viruses.

     T Theoharides, COVID-19, pulmonary mast cells, cytokine storms and beneficial action of luteolin. Biofactors, 2020, Apr 27:10.1002/biof.1633

This study from Boston relies on a previous study from Beijing. In a two-step screening assay to detect small molecules of herbal origin that interfere with the entry of the SARS virus into the hosts cells, one of the most efficient molecules to bind with the surface spike proteins found was luteolin.

     Ling Yi, Zhengquan Li, Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J of Virology, 2004, 11334-11339.