*Ginkgo biloba*: A Potential Anti-Cancer Agent

*Jian-Shu Lou, Die Hu, Hao-Jie Wang, Li-Ping Zhao, Jun-Hu Hu and Zhao-Huang Zhou*

### **Abstract**

*Ginkgo biloba* is generally considered as safe herbal extract in clinical application. Ginkgo Folium is a living fossil plant, which has been used in record by over few thousands of years. The extract of *G. biloba*, has been used extensively for the treatment of diseases related to the central nervous system and psychiatric disorders. Recently, different lines of evidence indicated that *G. biloba* exhibited anti-cancer effects. The potential therapeutic effect may due to antioxidant, anti-angiogenic and gene regulatory actions. In addition, Ginkgo Folium was studied in pharmacodynamic interactions induced by herb-drug interactions. These studies indicated that *G. biloba* usually exhibits synergistic effect. The extracts derived from *G. biloba* exhibits promising anticancer effect, including flavonoids, ginkgolide, and phenolic acids etc. This chapter will discuss the anticancer effect and mechanism of extracts derived from various parts of *G. biloba*, the possible usage as an adjuvant therapy in cancer treatment, and the development of *G. biloba* as potential novel anticancer drugs.

**Keywords:** *Ginkgo biloba*, cancer, natural products, herbal extract

### **1. Introduction**

Almost everyone talks about cancer discoloration, and no matter what kind of cancer it is, it can be life-threatening. But fortunately, cancer can also be treated, in addition to mastering the rhythm of life, you can also choose Chinese herbal medicine to strengthen the immunity and enhance the ability to anti-cancer. The active gradients from several plants have anticancer effect, such as Elemene, vincristine and ginsenosides [1–6]. Elemene, isolated from the volatile oil of traditional Chinese medicine Curcuma wenyujin, has broad-spectrum anticancer activities and mild side effects. Vincristine is derived from periwinkle, which is used for the treatment of acute lymphoblastic leukemia, breast cancer. Ginsenosides is extracted from ginseng. Ginseng has been regarded as a famous traditional Chinese medicine since ancient times. After treatment with ginsenosides, ginsenosides inhibited cancer cell proliferation, invasion, and migration in several cancers, such as breast, brain, liver, gastric, and lung cancer [5].

In recent years, more and more studies have shown that *G. biloba* also has antitumor effect*s. G. biloba* appeared on earth more than 200 million years ago and is

the only living species in the order Ginkgoales [7–9]. Once *G. biloba* was growing everywhere on earth, but it became nearly extinct during the last ice age, and only survived in Asia. *G. biloba* has been used as a medicinal plant for a long time. It was firstly recorded in "Shennong Ben Cao Jing, but the medicinal value of ginkgo leaves recorded from the Song Dynasty. The medical use of *G. biloba* was first recorded in "Ben Cao Gang Mu" by Li Shizhen in Ming Dynasty [10]. *G. biloba* leaves are fanshaped, flat, and have an indentation in the middle, giving birth to a species name "Biloba," a Latin word meaning bi-lobed [11]. Male flower pollens are carried by the wind to the female tree, which produces ovules that fertilize and grow into seeds. *G. biloba* takes 15 to 20 years to produce fruits, which have a rancid, nasty odor. However, the seeds contain certain mild toxic chemicals [12–14]. *G. biloba* has been a beloved plant in Asian countries as an ornamental tree in the gardens and as a medicinal plant, particularly in China, Korea, and Japan [15, 16].

Scientists from Japan and Germany made pioneering and important contributions to research and development. The development history of *G. biloba* fully embodies the determination of innovation and has become a model for the research and development of traditional Chinese medicine and botanic medicine. In 1929, the Japanese first isolated a flavonoid from *G. biloba* leaves [17]. In the 1960s, Dr. Schwab firstly extracted the active ingredients (ginkgo flavone and terpenoid lactone) from Chinese *G. biloba* leaves, which were processed into tablets. These active ingredients quickly became the first world's plant medicine, which were listed as the third generation of *G. biloba* leaves preparation. In 1972, Dr. Willmar Schwabe Company developed EGb761, a patent extract of *G. biloba* leaves. EGb761 contains 24% flavonoids and 6% terpenoids, which is widely used today [18]. From the 1920s to the 1930s, Chinese herbal medicine research upsurge, medical scholars began to analyze the chemical components of G. biloba, pharmacodynamics and toxicology research, with G. biloba tablet, known as the first generation of preparation. In the 1970s, Germany, France and other European countries carried out in-depth research on *G. biloba* leaves. Flavonoids and lactones extracted *G. biloba* have therapeutic effects on cardiovascular and cerebrovascular diseases [19]. In the 1990s, Professor Xie Delong, director of Shanghai Institute of Traditional Chinese Medicine, discovered a safer and more effective combination than the German ginkgo leaf invention patent, and innovated the process to raise the clear effective component of the extract to more than 50%, which was listed as the fifth generation of ginkgo leaf preparation.

At present, flavonoids (quercetin, kaempferol, isorhamnetin, lignin, etc.) and terpenoids (ginkgolide A, Ginkgolide B, ginkgolide C, ginkgolide J, etc.) have been found to be active pharmacological components in *G. biloba* [20]. It is recorded in Chinese Pharmacopoeia that *G. biloba* has the effects on promoting blood circulation and removing stasis, clearing collaterals and relieving pain, strengthening lungs and relieving asthma, removing turbidity and lowering lipids, and is used to treat blood stasis and blocking collaterals, chest paralysis and heartache, stroke hemiplegia, lung deficiency, cough and asthma, hyperlipidemia and other diseases [21–23]. In recent years, studies have also found that the pharmacological effect of *G. biloba* lies in the synergistic effect of various components, rather than a component to play a determined role. Studies have shown that *G. biloba* extract plays a significant role in the treatment of Alzheimer's disease, neurodegenerative diseases, brain dysfunction, eye diseases, cardiovascular diseases and other diseases. Moreover, recent studies have shown that extract from different part of *G. biloba* may also be useful in treating cancer [24].
