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GINGKO

by Attilio D'Alberto

Introduction

The Gingko tree (Gingko Biloba L. of the Gingkoaceae family) is generally recognized as one of the oldest trees in the world having survived a stage of plant evolution that was destroyed during the last ice age. The modern Gingko species appears to have spread over China and the rest of the world from a mountain range in Southwest China, the only place identified by botanists where the Gingko could have survived the ravages of glaciations and global flooding that accompanied the last ice age (Fruehauf 1997, p13).

To the ancient Chinese, the Gingko tree had an important Yin-Yang quality. It was said that only if the male and female trees were planted together there would be seeds; or if the female tree was planted by the side of a pond where it could reflect itself in the water, there would also be seeds. The tree was also a symbol of longevity and vitality, probably owing to the fact that it can grow to a height of 100-122 feet, have a diameter of 3-4 feet and live for several millennia.

In Traditional Chinese Medicine (TCM), the Gingko is more commonly recognized for its seed or fruit or nut (Semen Gingko Bilobae) as the most precious medicinal part. It has been used by the Chinese for many thousands of years but it was not until 1367 that it was formally recognized as having a medicinal quality when it was published in the Materia Medica of Everyday Food Items (Riyong Bencao) by Wu Rui. Although they have not featured as prominently in the Chinese Materia Medica as the seeds, the Gingko leaves (Folium Gingko Bilobae) have been used just as early and extensively as indicated by oral tradition and written sources. The Gingko leaf first received a formal entry into the Chinese Materia Medica in 1505 in Liu Wentai’s Compilation of Essential Items of the Materia Medica (Bencao Pinhui Jingyao) (Fruehauf 1997, p14). It has been the Gingko leaf that has attracted the attention in the West where it has been the subject of intense pharmacological and clinical studies over the past 30 years.

The aim of this essay is to discuss the medicinal properties, actions, indications and clinical applications of Gingko Biloba as used by TCM and to examine its modern scientific research.

Semen Gingko Bilobae (Bai Guo)

In TCM, the Gingko seeds are known as Bai Guo (literally ‘White Fruit’) and are grown throughout China where they are harvested between October to November when the seeds are ripe. The properties and flavors attributed to Bai Guo are sweet, bitter, astringent, neutral and slightly toxic and the channels it enters are the Lung and Kidney. Because Bai Guo is astringent and descending in nature, it can be used to treat cough and asthma with copious sputum caused by Phlegm obstructing the chest leading to Rebellious Lung-Qi, in either Cold or Heat Syndromes. It can remove Dampness and strengthen the Spleen-Qi making it an important herb in treating leukorrhea due to either Spleen-Deficiency (manifested by copious thin white vaginal discharge) or by the downward flow of Damp-Heat (thick yellow discharge with a foul smell accompanied with an itching of the vulva). Bai Guo also has the ability to stabilize the lower-Jiao and relieve symptoms such as frequent urination, incontinence and spermatorrhea by consolidating the Kidney-Qi (Chen 1997, p180).

The dosage for Bai Guo is 4.5-9g. It is used in its raw form for treating Phlegm and clearing Heat and processed for stopping wheezing and restraining urine. Because of its slight toxicity, if the raw form is prescribed then the dosage must be reduced and it should not be used for a long period of time. The husk of the seed is removed first and then the seed is crushed before use. Good quality is white, full and round (Bensky and Gamble 1993, p390).

Bai Guo is contraindicated in cases of excess and should be used with caution whenever there is viscous sputum that is difficult to expectorate. Symptoms of overdose include headache, fever, tremors, irritability and dyspnoea, which can be relieved using an antidote of 60g of boiled raw Radix Glycyrrhizae Uralensis (Gan Cao) or 30g of boiled gingko shells. However, an overdose can be avoided by using the hard shells and the thin linings of the seeds when using this herb in a decoction (Bensky and Gamble 1993, p390). In more serious cases of toxicity, the patient may display such symptoms as vomiting, drowsiness, fear, convulsions, cyanosis, constriction/ dilation of pupils, delayed reaction to light, abdominal pain and diarrhoea, increase of neutrophils and white blood cell count, and flaccid paralysis (Yeung 1996, p44). One such case of an overdose was reported by Miwa, Iijima, Tanaka and Mizuno (2001, p280) where the patient displayed symptoms of frequent vomiting and generalized convulsions after consuming 70-80 gingko seeds.

There are two main formulas in which Bai Guo is used. The first is the ‘Arrest Wheezing Decoction’ (Ding Chuan Tang). The action of this decoction is to disseminate and redirect the Lung-Qi, stop wheezing, clear Heat and transform Phlegm (Bensky and Barolet 1990, p300-1). The second formula is the ‘Change Yellow (Discharge) Decoction’ (Yi Huang Tang). The action of this formula is to strengthen the Spleen, dry Dampness, clear Heat, and stop the vaginal discharge (Bensky et al 1990, p370-1). A further analysis of these formulae can be found in Appendix 1.

Bai Guo contains a number of chemical components: gibberellin, cytokine-like substances, ginkgolic acid, hydroginkgolinic acid, bilobol, ginnol, aspartine, calcium, phosphorus and iron. Modern research on Bai Guo’s effects is very limited, which is probably due to the West’s interest in the medicinal value of the Gingko leaves rather than the seeds. However, ginkgolic acid has shown to have a very strong in vitro inhibitory effect against Mycobacterium tuberculosis, but has not been useful in in vivo studies. Preparations of Bai Guo have shown an in vitro inhibitory effect against the growth of bacteria such as Staphylococcus aureus, C. diphtheriae, E. coli and Salmonella typhi (Bensky et al 1993, p390). Bilobol has shown to cause paralysis of the intestines of rabbits whilst contracting the uterus and lowering blood pressure (Yeung 1996, p44).

Folium Gingko Bilobae (Yin Xing Ye)

From a TCM perspective, the Gingko leaf is classified in a similar fashion to the seed. Its property is neutral; its flavors sweet, bitter and astringent; its channel affinity extends beyond the Lung into the Spleen, Stomach and Heart (Fruehauf 1997, p14). Its actions are astringing the Lung to calm asthmatic wheezing and phlegm; halting diarrhea by transforming Dampness; nourishing the Heart treating stuffiness in the chest, pain and palpitations; and for absentmindedness, forgetfulness, depression, dizziness and premature senility. Thus, it can be used in syndromes of Heart Blood and Qi-Stagnation, Lung-Qi constraint and Kidney-Essence Deficiency (Holmes 1996, p197).

Yin Xing Ye can be decocted or infused for 15-20 minutes (6-12g) or used as a tincture (2-4ml). It should be used with caution as it may cause mild side effects such as dizziness, headache, fatigue, gastric or chest discomfort, loss of appetite, constipation or diarrhoea (Holmes 1997, p280).

The Gingko leaves contain a number of active constituents including bioflavonoids such as the flavonoid glycosides kaempferol, quercetin, and isorhamnetin; flavones; and organic acids. Novel diterpene lactones, unique to Gingko, are currently the focus of intensive pharmacological and clinical research. These include the ginkgolides (A, B, C, and M) and bilobalide (Foster 1996, p4). Virtually all of the 400 pharmacological and clinical studies published have involved a specific standardised extract (EGb 761) developed and researched in Germany, which contains 24% flavone glycosides, 5-7% terpene lactones and 2.6-3.2% bilobalide.

The pharmacokinetic properties of EGb 761 have proved difficult to ascertain due to the complexity of the extract. Studies in healthy human volunteers have shown that the flavonol glycosides are absorbed in the small intestine; reach peak plasma concentrations within 2-3 hours; have an elimination half-life of 2-4 hours; and are completely eliminated 24 hours after ingestion of the extract. The absolute bioavailabilities of Ginkgolides A and B are practically complete, regardless of the dosage, whereas that of Gingkolide C is very low (DeFeudis 1998, p21). Ginkgolides A and B reach peak plasma concentrations 1.4-2 hours after administration and have a half-life of 3.9 and 7 hours respectively. The bioavailability of bilobalide is 72% with a half-life of 3.2 hours after oral administration. The ginkgolides are eliminated via the urine, ginkgolides A and B mainly in-unchanged form (DeFeudis 1998, p22).

EGb 761 has been shown to be beneficial in a wide range of physiological dysfunctions and pathological conditions, including those involved with circulation, blood conditions, metabolism, and immune function. The American Botanical Council (2001, www.herbalgram.org/herbal_e/gingko.html) states that the Commission E (a German governmental body established to evaluate the safety and efficacy of herbs) has found the following pharmacological effects to have been established experimentally:

· Improvement of hypoxic tolerance (especially in cerebral tissue);

· Inhibition of the development of traumatically or toxically induced cerebral oedema, and acceleration of its regression;

· Reduction of retinal oedema and of cellular lesions in the retina;

· Increased memory performance and learning capacity;

· Improvement in the compensation of disturbed equilibrium;

· Improvement of blood flow, particularly microcirculation;

· Improvement of the rheological properties of the blood;

· Inactivation of toxic oxygen radicals (flavonoids);

· Antagonism of platelet-activating factor (PAF) (ginkgolides); and

· Neuroprotective effect (ginkgolides A and B, bilobalide).

Thus, the Commission E has approved the internal use of the Gingko extract for the following conditions:

· For symptomatic treatment of disturbed performance in organic brain syndromes (memory deficit, disturbances in concentration, depression, dizziness, tinnitus, headache, dementia syndromes);

· Improvement in pain-free walking distance in peripheral arterial occlusion (intermittent claudication); and

· Vertigo and tinnitus of vascular and involutional origin.

The World Health Organization (1999, p158) reiterated the Commission E approved uses adding Raynaud’s disease (intermittent blue coloring of the extremities due to restricted blood flow with no known direct cause), acrocyanosis (i.e. Crocq’s disease: persistently poor circulation to hands and sometimes the feet, resulting in cold, blue, sweaty condition), and post phlebitis syndrome (painful swelling of the vein).

EGb 761 is available in liquid or solid forms for oral intake at an average dose of 120mg taken 2-3 times daily, and should be taken consistently for at least 12 weeks to be effective. Side effects include mild gastrointestinal complaints and allergic skin reactions in rare cases. In terms of drug interactions, Gingkolide B has an inhibitory effect on platelet-activating factor (PAF), thus it has the ability to potentate the effects of anticoagulants, thrombolytics, antiplatelet agents and MAO inhibitors (Kleijnen and Knipschild 1992, p1136-9). It can also increase the risk of bleeding with some cephalosporins, valproic acids and NSAIDS.

There are a number of similarities between the TCM and modern biomedical perspective for their uses of the Gingko seed and leaf. The Gingko leaf is used in TCM for Heart-Qi and Blood Stagnation, corresponding to its use for peripheral arterial occlusion, angina pectoris, cerebral ischaemia, thrombosis and hypercholesterolaemia; Kidney-Essence Deficiency refers to its use for dizziness, tinnitus, depression, absent-mindedness, memory loss, cerebral insufficiency (neurasthenia), poor vision (retinal/macular degeneration) and premature senility (Alzheimer’s, Parkinson’s disease); and Lung-Qi constraint signals its use in asthma and chronic bronchitis. The seed is used to expel Phlegm and stop wheezing, which corresponds to its demonstration as having an antituberculotic and antibiotic effect in vitro.

Conclusion

Judging by the number of different effects Gingko has demonstrated in numerous clinical studies, it is possible to see why it is so widely used today in treating many different pathological conditions. Another reason for its increasing popularity is because it is natural and not manufactured and has shown very minimal side effects. Perhaps the ongoing clinical studies will show Gingko to have a few more surprises, as what is known about it today is in no way complete. Either way, it is a fascinating substance that will continue to treat people for a long time to come.

Appendix (adapted from Bensky and Barolet 1990, p300-301 and 370-371)

1. Arrest Wheezing Decoction (Ding Chuan Tang)

This formula is indicated where there is coughing and wheezing with copious, thick and yellow sputum, labored breathing, fever and chills, a greasy, yellow tongue coating, and a slippery, rapid pulse.

Semen Gingko Bilobae (Bai Guo) 9g (or 21 pieces)

Herba Ephedrae (Ma Huang) 9g

Fructus Perillae Frutescentis (Su Zi) 6g

Radix Glycyrrhizae Uralensis (Gan Cao) 3g

Flos Tussilaginis Farfarae (Kuan Dong Hua) 9g

Semen Pruni Armeniacae (Xing Ren) 4.5g

Cortex Mori Albae Radicis (Sang Bai Pi) 9g

Radix Scutellariae (Huang Qin) 4.5g

Rhizoma Pinelliae Ternatae (Ban Xia) 9g

The wheezing that this formula is used for is caused by Wind-Cold constraining the exterior and Phlegm-Heat burning in the interior. This often occurs in patients who have a constitutional tendency towards excessive Phlegm who then contract Wind-Cold. This causes an obstruction of Lung-Qi, disrupting its dispersing and descending function so that the constrained Qi transforms into Heat. This produces thick, yellow sputum that is difficult to expectorate.

Ma Huang unblocks and redirects the Lung-Qi down, stops the wheezing, and releases the exterior Wind-Cold. Bai Guo transforms the Phlegm, stops the leakage of Lung-Qi, stops the wheezing, and prevents Ma Huang from causing excessive dispersion and depletion. Xing Ren reinforces Ma Huang’s actions in expanding the Lung and stopping the wheezing. Su Zi, Ban Xia and Kuan Dong Hua assist in directing the Rebellious-Qi down, stopping the wheezing and expelling the Phlegm. Sang Bai Pi and Huang Qin drain Heat from the Lung and stop the wheezing and coughing. Gan Cao harmonises the actions of the other herbs in the formula.

2. Change Yellow (Discharge) Decoction (Yi Huang Tang)

This formula is indicated for chronic vaginal discharge that is yellowish-white, viscous, and fishy-smelling with other signs and symptoms like a pale-yellow complexion, dizziness, heavy sensation in the head, reduced appetite, loose stools, delayed menstruation with pale blood, pale tongue with thin white coating, and a soft, slippery pulse.

Dry-fried Radix Dioscoreae Oppositae (Chao Shan Yao) 30g

Dry-fried Semen Euryales Ferocis (Chao Qian Shi) 30g

Cortex Phellodendri (Huang Bai) 6g

Semen Plantaginis (Che Qian Zi) 3g

Semen Gingko Bilobae (Bai Guo) (crushed) 10 kernels

This formula is used for Spleen-Qi Deficiency with Dampness where the Dampness becomes constrained, transforms into Damp-Heat and drains downward. The yellowish-white, viscous and fishy-smelling vaginal discharge is caused by the combination of deficient Spleen-Qi and Damp-Heat. The Dampness damages the Spleen’s function in transforming and transporting so that the clear Yang cannot rise, which manifests as a pale-yellow complexion, heavy sensation in the head, reduced appetite and loose stools. The deficient Spleen will also mean that it cannot generate sufficient Qi and Blood causing menstruation to become delayed with pale blood.

Chao Shan Yao strengthens the Spleen and stabilizes the lower-Jiao and Essence, which are associated with vaginal discharge. Huang Bai and Che Qian Zi drain Damp-Heat from the lower-Jiao via the urine, which will eventually stop the discharge. Chao Qian Shi and Bai Guo help to stabilize the lower-Jiao and restrain the discharge.

References

American Botanical Council. (2001). Gingko Biloba Extract. www.herbalgram.org/herbal_e/gingko.html (31/03/01).

Bensky, D. and Barolet, R. (1990). Chinese Herbal Medicine: Formulas & Strategies. Seattle: Eastland Press.

Bensky, D. and Gamble, A. (1993). Chinese Herbal Medicine: Materia Medica. (Rev. ed.) Seattle: Eastland Press.

Chen, P. (1997). Chinese Herbs and Compatibility. Beijing: Science Press.

DeFeudis, F. V. (1998). Gingko Biloba Extract (EGb 761): From Chemistry to the Clinic. Wiesbaden: Ullstein Medical.

Foster, S. (1996). Gingko; Gingko Biloba. Texas: American Botanical Council.

Fruehauf, H. (1997). ‘The Gingko. Cultural Background and Medicinal Usage in China’, Journal of Chinese Medicine, 55, p13-16.

Yeung, H.C. (1996). Handbook of Chinese Herbs. (2^nd ed.) California: Institute of Chinese Medicine.

Holmes, P. (1996). Jade Remedies: A Chinese Herbal Reference for the West. (vol. 1). Colorado: Snow Lotus Press.

Holmes, P. (1997). The Energetics of Western Herbs. (vol. 1). (3^rd ed.) Colorado: Snow Lotus Press.

Hsu, H.Y. (1986). Oriental Materia Medica: A Concise Guide. Connecticut: Keats Publishing Inc.

Kleijnen, J. and Knipschild, P. (1992). ‘Gingko Biloba’, Lancet, 340, p1136-9.

Miwa, H., Iijima, M., Tanaka, S. and Mizuno, Y. (2001). ‘Generalised Convulsions after Consuming a Large Amount of Gingko Nuts’, Epilepsia, 42, (2), p280-281.

Murray, M. T. (1995). The Healing Power of Herbs. (2^nd ed.) Rocklin: Prima Publishing.

Pizzorno, J.E. and Murray, M.T. (1999). Textbook of Natural Medicine. (vol. 1). (2^nd ed.) London: Churchill Livingstone.

Yan, X., Zhou, J. and Xie, G. (1999). Traditional Chinese Medicines: Molecular Structures, Natural Sources, and Application. Aldershot: Ashgate Publishing.

WHO Geneva. (1999). WHO Monographs on Selected Medicinal Plants. (vol. 1). Malta: WHO Library Cataloguing Publication Data.

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