The Anti-HBV, Anti-Hepatoma and Hepatoprotective Effects of the Euphorbiaceae Plant Yexiazhu (Phyllanthus urinaria)

The Chinese herb Zhenzhucao (pearl grass) is the dried whole herb, or whole herb with root, of Phyllanthus urinaria L. of the spurge family (Euphorbiaceae), produced mainly in Guangdong, Guangxi, Sichuan, Jiangxi, Fujian and Zhejiang. It is named for its pearl-like fruits beneath the leaves. It was first recorded in the herbal material manual Shengyao Caoxing Beiyao, compiled by He Jian during the Kangxi reign of the Qing dynasty. TCM uses it to treat dysentery, diarrhea, jaundice, edema, heat strangury, stone strangury, red eyes, night blindness, welling-abscesses and swellings, and venomous snake bites.

The Shengyao Caoxing Beiyao records that it “treats childhood gan-eyes and gan-accumulation; decoct with meat for food, or use the decoction for washing; it also treats loss of breast milk and is most effective for rice-gan.” The so-called “gan-eyes” is an eye disease characterized by dry, light-averse eyes, loss of luster of the white of the eye, pannus on the cornea, which may ulcerate and perforate to form crab-eye or spiral protrusion, or even collapse of the eyeball with blindness, accompanied by thirst, diarrhea, abdominal distension and prominent veins. This condition corresponds mostly to what modern medicine calls keratomalacia, caused by vitamin A deficiency. The childhood gan-accumulation of ancient TCM is similar to the modern concept but also differs; childhood tumors were also regarded as gan-accumulation in ancient TCM.

Modern pharmacological research has found that the most important actions of Yexiazhu (pearl grass) are anti-hepatitis B virus, anti-hepatocyte injury, anti-primary hepatocellular carcinoma, and anti-HIV. There is a considerable body of Chinese and foreign research literature on Yexiazhu's antiviral and anti-tumor actions. For example, Thyagarajan and Xu Dawen et al. have both reported that the water extract of Yexiazhu can inactivate hepatitis B virus; Agarwal and Venkateswara et al. reported that Yexiazhu can counteract hepatocyte injury; Verkanteswaran reported that the water extracts of Yexiazhu inhibit HIV-IRT by 50% and 96% respectively; Katagata Takahiro et al. isolated the compound mauitianic acid A from Yexiazhu, which showed inhibitory activity against HIV-IRT. Other animal experiments have confirmed that lignans isolated from Yexiazhu have anti-tumor, anti-mitotic and antiviral activities, and can kill the human hepatoma cell line SMMC7721 and inhibit its proliferation. In addition, a decoction of Yexiazhu inhibits beta-hemolytic streptococcus, Staphylococcus aureus, Escherichia coli, Shigella flexneri, Salmonella typhi and Pseudomonas aeruginosa.

These pharmacological experiments confirm that the ancient TCM use of Yexiazhu to treat jaundice, edema, diarrhea and welling-abscesses was correct. TCM holds that Yexiazhu is sweet and bitter in taste and cool in nature, entering the liver and lung meridians; its main actions are to disinhibit dampness and resolve jaundice, clear heat and detoxify, brighten the eyes, and disperse accumulation. Most of these TCM disease names relate to hepatobiliary disorders.

When TCM uses Yexiazhu to disinhibit dampness and resolve jaundice (i.e., to treat jaundice hepatitis and hyperbilirubinemia), it is often combined with other water-disinhibiting, jaundice-resolving herbs such as Yinchen (Artemisia capillaris), Zhizi (gardenia), Jinqiancao (coin herb), Huzhang (Polygonum cuspidatum) and Tianjihuang (Hypericum japonicum). Yexiazhu also diureses and expels stones; when TCM uses it for gallstones and urinary stones, it is often combined with stone-expelling herbs such as Jinqiancao, Haijinsha (Lygodium spores) and Jineijin (chicken gizzard lining). Yexiazhu is also widely used to treat diarrhea; for that it is often combined with herbs of similar effect such as Huanglian (Coptis), Huangbo (Phellodendron), Qinpi (ash bark), Baitouweng (Pulsatilla) and Machixian (purslane).

Yexiazhu clears heat and detoxifies, and cools the blood and reduces swelling, so it is often used for venomous snake bites and welling-abscesses and sores. Used for primary liver cancer and gallbladder cancer, Yexiazhu not only protects the liver, benefits the gallbladder and resolves jaundice, but also inhibits the growth of cancer cells; it is therefore an important herb in treating liver and gallbladder cancer.

Yexiazhu also treats eye diseases, mostly red, swollen eyes from liver-heat ascending, and childhood gan-eyes; it may be used alone or combined with Juhua (chrysanthemum) and Juemingzi (cassia seed).

But Yexiazhu is bitter-cold and injures the stomach, so when treating patients with weak spleen and stomach, aversion to cold and yang deficiency, it must be combined with corresponding spleen-stomach-fortifying and yang-supporting herbs such as Baizhu (Atractylodes) and Fuzi (aconite). In addition, local herbal annals in various regions record Yexiazhu for ascites caused by liver cancer, nephritis and other conditions.

This herb is mostly added to decoctions, and animal experiments also show that the water extract of Yexiazhu has the best efficacy. The adult dose is 10–30 g per day; when treating liver cancer, the dose may be doubled, and it should be combined with other anti-hepatoma herbs such as Biejia (turtle shell), Baihuasheshecao (Oldenlandia), Banbianlian (Lobelia), Banzhilian (Scutellaria barbata), Chuipencao (Sedum sarmentosum), Shuihonghuazi (Polygonum orientale fruit) and Xianhecao (Agrimonia), and should be paired with bleeding-preventing medicines such as Yunnan Baiyao.