Perilla (Perilla frutescens Britt.), a traditional Chinese herb, has recently received special attention because of its beneficial effects in the treatment of some kinds of allergic reactions without the side effects associated with some other used antiallergy medicines. In this chapter, the authors present a review of the problem of allergy and the current favorable evidence for the use of Perilla products towards its resolution.
- 1 The Allergy Problem
- 2 The Treatment of Allergy
- 3 Application of Perilla Leaf Extract for Allergy
- 4 Use of Perilla Oil for Allergy
- 5 The Possible Mechanisms of Perilla in the Treatment of Allergy
- 6 Conclusion
The Allergy Problem
Allergy is an abnormal immune reaction of the body to allergens such as pollen, dust, certain foods, drugs, animal fur, animal pets, animal excretions, feathers, microorganisms, cosmetics, textiles, dyes, smoke, chemical pollutants and insect stings. Certain conditions such as cold, heat, or light may also cause allergic symptoms in some susceptible people. Some allergens are just specific to some individuals but not to others. Allergens may act via inhalation, ingestion, injection or by contact with the skin. The resulting allergy may cause the victim to have a medical problem such as hay fever (allergicrhinitis), or atopic dermatitis (eczema), or allergic asthma, with symptoms ranging from sneezing, rhinorrhea, nasal itch, obstruction to nasal air-flow, loss of sense of smell, watery and itching eyes as in allergic rhinitis; and skin itching, skin redness and skin lesion as in atopic dermatitis. Allergic patients suffer not only irritating symptoms but also an impairment of the quality of life.
In 1989 allergy diseases affected 10% of the world’s population (). Today, allergy is even more common. It is now the most wide spread immunological disorder in humans, and the most prevalent and rapidly increasing chronic health problem, particularly in the industrialized countries where allergy affects one in four individuals. Furthermore allergy also causes a socioeconomic problem resulting in huge economic losses. In the U.S. alone it costs billions of dollars per year ().
In the U.S. an estimated 20% or more of its population is allergic to something (). Allergic rhinitis alone affects 10-15% of the U.S. population (). The incidence of allergic asthma in the U.S. rose by 60% between 1979 and 1989 (). In England an investigation showed that the reported prevalence of asthma had risen from 4.1% in 1964 to 10.2% in 1989, hay fever from 3.2% rose to 11.9%, and eczema from 5.3% rose to 12% in the same period (). In Central Europe, pollinosis alone affects 10 percent of its population (). In Sweden, more than one in three adults and 40% of children suffer from allergy, and the number of allergy patients has doubled over the last ten years and continues to increase (). In Finland, 20-30% of young adults have the allergic symptoms (rhinorrhea), and about 20% of aged 0 to 6 year children have the skin eruption symptom (). In Australia, asthma affects as many as 20% of children and 10% of adults (). In Japan, an investigative data published by the Ministry of Welfare of Japan showed 34% of its population suffered from some kinds of allergies, and mostly among children from the age of 0 to 4 ().One-third of infants born in Japan are diagnosed as atopic ().
One main cause winch contributed to the increase in allergy incidence is the change of living environment and the extension of air pollution which is becoming more and more serious all over the world. In Japan, allergic rhinoconjunctivitis was found to be more prevalent in individuals living near motorways than in cedar forests. A recent study in Finland showed that admissions to hospital with severe asthma correlated with atmospheric levels of nitrogen dioxide (). In China, the prevalence of asthma is greater in the more modernized area than in the less developed area ().
O n the other hand, as a result of the affects of air pollution, the climatic change of global warming is likely to have significant effects on the distribution and abundance of allergenic plants. This impact on natural ecosystems is likely to be greatest in southern and Mediterranean Europe and in northern Scandinavia. These changes will alter the severity of pollen seasons and will have wide ranging implications for the incidence of pollinosis ().
However, the prevalence of allergy in China is generally much lower than in western countries. Hay fever, the leading allergic disease in the West, is not common in China and some other Asian countries (). It is interesting to investigate whether this difference is due to racial predisposition or environmental factors; or may partly be attributed to the popularity of the application of traditional Chinese medicines in China.
The Treatment of Allergy
The treatment of allergic diseases has benefited from the gradual understanding of allergy mechanisms. Allergic reaction is due to a change in the immunoreactivity of an individual. When the allergen is presented to T-helper cells, B-lymphocytes will overproduce allergen-specific IgE antibodies. In the case of allergen contact, IgE bound to mast cells leads to mast cell activation and degranulation. As a result, mast cells release abnormal amounts of mediators such as histamine, PAF (platelet-activating factor), leukotrienes, prostaglandin D. These mediators will dilate blood vessels, increase permeability of small blood vessels, stimulate nerve endings, stimulate secretion of mucus in airways, or constrict bronchial airways, so as to induce local inflammation and cause various immediate symptoms or chronic symptoms.
In addition, cytokines such as TNF (Tumor Necrosis Factor) were recently found to be linked with allergic reaction. Indeed, plasma TNF levels are elevated in the serum of patients with atopic dermatitis, and the levels are tightly correlated with plasma histamine (). Furthermore, TNF will reversely stimulate the immune cells to produce more mediators (). It is now accepted that, allergy pathogenesis is involved in multifactors including hereditary, environmental, and immunological factors.
The treatment of allergic diseases is mainly based on allergen avoidance, public health education, the use of chemotherapy (therapy using any synthetic pharmaceutical compound), traditional herbal therapy, immunotherapy or an herbal immune regulator. In this post, Perilla is advanced as a herbal immune regulator.
If the allergens can be identified, allergy may be treated simply by avoiding the offending agents. Allergen avoidance has always been seen as the first choice to be tried and the most effective treatment, but preventing exposure to some common environmental substances such as house dust mite, and pets allergens, is seldom possible. As mentioned above the main cause of the allergic reaction is air pollution, therefore it is virtually impossible to prevent outdoor allergens exposure completely. Furthermore, even when an allergen, such as a pet is removed from a patient’s environment, the benefit may take several weeks or months to be perceived ().
Public Health Education
Public health educational campaigns are helpful in promoting self-medication and rational and economic treatment of allergy. For example, in Sweden the year 199.5 was proclaimed as the Allergy year by five related national organizations for improving quality of life of allergy sufferers () and in Finland, a similar campaign was undertaken by Finnish community pharmacists ().
As a main measure, medicine therapy plays an important role in allergy treatment. But with today’s medicines such as antihistamine, corticosteroids, sodium cromoglycate and so on, it is still symptomatic (). The symptoms of allergic diseases are caused by various factors and are different in individuals, and therefore therapy must be varied accordingly. Present medicines can cause side effects such as osteoporosis, diabetes, weight gain, ulcer and resistance to the corticosteroids. Although new application techniques have dramatically decreased the unfavorable side effects, some newer effective approaches to allergy treatment without side effects are still eagerly awaited by sufferers and physicians.
Immunotherapy is a specific form of controlled allergen admission that changes immunoactivity into allergen tolerance. It has been used for more than 80 years but still represents a controversial treatment of allergic diseases (). It is appreciated that the efficacy of allergen immunotherapy is currently very low. Severe symptomatic reactions occasionally may occur, especially in asthmatic patients. In certain countries (the UK and the Scandinavian countries) the use of immunotherapy has been greatly curtailed due to adverse reactions (International Rhinitis Management Working Group, 1994).
Traditional Chinese Medicine (TCM)
With thousands of years of experience in treating diseases with natural materials, TCM still plays an important role in the health-care system of modern China and is officially recognized not only in China, but also in Japan and in some other eastern and southeastern Asian countries which have the sake cultural tradition (). People there still prefer to use traditional herbs for the treatment of allergy. There are several TCM prescriptions effective for allergic symptoms (). Some of them are listed in Table Some traditional Chinese herb prescriptions for allergy. Among them, the Minor-Bupleurum-Combination with Pinellia-Magnolia Combination (Saibokuto), consisting of ten herbs including Perilla and the Ephedra-Magnolia-Combination containing Perilla, have been traditionally used for the treatment of bronchial asthma. Studies showed that Saibokuto, and Minor-Blue-Dragon-Combination (Syoseiryuto) clinically exhibit inhibitory effects on type I allergic reaction () and Saibokuto was found to inhibit histamine release and mast cell degranulation ().
Table Some traditional Chinese herb prescriptions for allergy
|Allergic Rhinitis and Pollinosis||Minor Blue Dragon Combination|
|Magnolia flower and Gypsum Combination|
|Ephedra and Apricot Seed Combination|
|Minor Bupleurum Combination with Pinellia and|
|Magnolia Combination (with Perilla)|
|Ephedra,Aconiti and Asarum Combination|
|Bronchial Asthma||Minor Blue Dragon Combination|
|Minor Bupleurum Combination with Pinellia and|
|Magnolia Combination (with Perilla)|
|Ephedra and Apricot Seed Combination|
|Minor Bupleurum Combination with|
|Ephedra and Apricot Seed Combination|
|Ephedra and Magnolia Combination (with Perilla)|
|Hoelen and Schizandra Combination|
|Urticaria||Minor Blue Dragon Combination|
|Bupleurum and Sc.hizonepeta Combination|
|Crab and fish poisoning||Perilla and Ginger Combination|
Furthermore, there has been increasing interest in western countries for TCM. British scientists achieved impressive results with a TCM prescription (Zemaphyte) containing 10 Chinese herbs for the treatment of severe atopic eczema (). Dr. Allan indicated in the FIP-CPA’93 (International Pharmaceutical Federation-Chinese Pharmaceutical Association) that most western medicines are single substances intended for a single well-defined disease. Complex diseases like eczema were not well served by western medicine but are often successfully treated with TCM (). Cooper indicated that the mechanism of action of Chinese herbal mixtures and their toxicities require further investigation, but may reveal hitherto unconsidered avenues (). Therefore, traditional herbs are a potential valuable source for obtaining effective medicines for the treatment of allergy.
Herbal Immune Regulators
In recent years, many researchers have been interested in elucidating the function of TCM as biological response modifiers or immune regulators. It has also been confirmed that some common vegetables or herbs contain nonnutritive components that may provide protection against chronic diseases including allergy and even some forms of cancer. ().
A research team led by Prof. Yamazaki of Teikyo University, Japan, reported about the screening of vegetables with immune regulating activity. Experiments in vivo and in vitro found that among 18 kinds of vegetables, Perilla and ginger were the most active in reducing TNF production and its activity, which is linked with the allergy and inflammation as mentioned above (Yamazaki, 1992). Based on these findings, Kosuna and Yamazalu have developed the new application of Perilla in the treatment of allergy (). On the other hand, it has also been found that Perilla seed oil rich in n-3 fatty acid (α-linolenic acid) is also said to have some benefit in the treatment of allergy and this is dealt with later in this post ().
Interestingly, these findings agreed with earlier reports on the application of Perilla and ginger mixture for the clinical treatment of asthma and chronic bronchitis (). Further reports trace back to the traditional use of Perilla leaf and seed for hundreds of years in the treatment of asthma () and some symptoms associated with what is now known as allergy. Also, the traditional method of cooking crab or shellfish with Perilla leaves, in order to prevent so called ” poisoning” existing in crab etc., might be re-evaluated as an effective way of preventing food allergy (IgE-mediated allergy) ().
Use of Perilla Oil for Allergy
Bjorneboe et al. () reported that dietary modifications involving supplementation with fish oil (rich in n-3 fatty acids) slightly favored the experimental group over the control group in the case of atopic dermatitis. Dietary Perilla oil, rich in n-3 fatty acids (which contain 54—64% linolenic acid) was also found to have some benefit in atopic dermatitis ().
Recent studies have indicated that the dietary α-linolenate/linoleate balance affected on the development of some chronic diseases including allergy (). Okuyama proposed that the excessive intake of linoleic acid and the changes in the essential fatty acid balance of diets have made our bodies hyperreactive to various allergens. The increase in the intake of Perilla oil will inhibit the production of leukottienes which is another important mediator causing allergy (). Therefore taking Perilla oil might be beneficial for the prevention and treatment of allergy.
Some recent patents have been published about the efficacy of Perilla oil for the treatment of allergy (Jpn. Patent Kokai Tokkyo Koho JP 290822,1992). In one study (Table Efficacy of Perilla oil in allergy) twenty four patients with atopic dermatitis patients (male 18, female 6, aged 5-32 years) were divided into four groups each taking different kinds of oil, 2-3 grams. The different oil groups had different ratios of n-6/n-3 fatty adds. After three months those taking Perilla oil had benefited significantly (Jpn. Patent KokaiTokkyo KohoJP 290822,1992). Ito et al. () also reported a pilot study on 6 atopic dermatitis outpatients treated with Perilla oil. These patients were given α-linolenic acid-enriched diet reducing the n-6 fatty acid (linoleic acid and arachidonic acid) intake and increasing the n-3 fatty acid (Perilla oil). After 40 days treatment the dermatitis improved in 3 patients. Results suggested that daily meals containing α-linolenic acid-enriched diet may have some benefit in the treatment of allergic diseases.
Table Efficacy of Perilla oil in allergy
|Patient Group||Intake Oil||n6/n3||Improvement % after|
|one month||two months||three months|
|1||Perilla oil 100%||0.22||33||50||83|
|3||Safflower oil 100%||382.5||0||0||17|
|4||Perilla oil 80%
Sesame oil 20%
Allergy has become a serious problem affecting health and social economy. New approaches to the treatment of allergy have been studied and developed. Based on the long-term use as a traditional Chinese herbal medicine, food spice and garnish; Perilla has now been confirmed in limited trials to have beneficial effects in the treatment of some allergy diseases such as hay fever and atopic dermatitis in children and adults, apparently without side effects. Preliminary mechanism studies support the use of Perilla products in the treatment of allergy and these are promising candidates for use in clinical double-blind, placebo-controlled trials.