The Anti-Cancer, Diuretic, Analgesic, Anti-Diarrheal, Acid-Suppressing, and Anti-Emetic Actions of Evodia (Wuzhuyu)

Wuzhuyu (Evodia) is the nearly ripe dried fruit of Tetradium ruticarpum (Evodia rutaecarpa), Evodia officinalis, or Evodia bodinieri of the Rutaceae family. It should not be left to fully ripen before harvesting; it is collected in July-August when the fruit is tea-green and the carpels have not yet separated. Pick whole fruit clusters before the dew has dried, without breaking the fruit branches. After harvesting, dry in the sun, rub by hand to detach the stalks, and winnow clean. If it rains, dry over low heat.

Ancient Chinese physicians used Evodia as a medicinal herb very early. It is included in China's earliest materia medica, the Shennong Bencao Jing, listed as a medium-grade herb. The Shennong Bencao Jing records that Evodia "mainly warms the middle and descends qi, stops pain, treats cough with counterflow, cold and fever, dampness and blood bi, expels wind evil, and opens the couli." Traditional TCM holds Evodia to be pungent and bitter in taste, hot in nature, slightly toxic, entering the liver, spleen, and stomach meridians. It disperses cold and stops pain, soothes the liver and descends qi, and warms the middle and dries dampness. It mainly treats epigastric and abdominal cold pain, jueyin headache, hernial pain, dysmenorrhea, beriberi swelling and pain, vomiting with acid regurgitation, and cold-damp diarrhea.

Evodia is a common herb for digestive diseases. TCM holds it effective for epigastric pain, diarrhea, and indigestion caused by deep cold and accumulated chill. The Mingbie Lu records Evodia as "removing phlegm-cold, abdominal colic, all cold accumulation that does not dissolve, sudden frights, heart and abdominal pain, counterflow qi, and benefiting the five viscera." The Yaoxing Lun records that Evodia "mainly treats heart and abdominal disorders, accumulated cold, qi binding below the heart, heart pain; treats cholera with tendon cramping, cold qi in the stomach, and vomiting, diarrhea, and abdominal pain that are unbearable; soothes stubborn bi throughout the body, undigested cold food, and benefits the large intestine's obstructing qi." The Shiliao Bencao records that Evodia "mainly treats dysentery, stops diarrhea, thickens the intestines and stomach, and makes people robust." In the Shanghan Lun, Wuzhuyu Tang combines Evodia with Renshen (ginseng) and Shengjiang (ginger) to treat jueyin headache and vomiting of frothy saliva. From these records, Evodia has a therapeutic role in digestive reactions such as indigestion, cholera, and dysentery.

Modern pharmacology has confirmed that Evodia has an anti-experimental-gastric-ulcer effect, inhibits spontaneous movement of gastric strips in experimental rats, and bidirectionally regulates small-intestine activity: at low concentrations it promotes intestinal peristalsis, while at high concentrations it inhibits it. This explains why Evodia can treat both indigestion and diarrhea.

Evodia also has good anti-tumor activity against digestive tumors. Modern experiments confirm Evodia has a marked cytotoxic effect on the gastric cancer cell line SGC-7901 and induces apoptosis. Evodia markedly inhibits growth of ascites-type mouse liver cancer HepA; evodine, at high, medium, and low doses, inhibits growth of mouse liver cancer H22. Evodia can also control ascites.

Animal experiments confirm that combining evodine with berberine (huangliansu) gives better anti-cancer and anti-emetic effects—and this pair is exactly the composition of the famous TCM formula Zuojin Wan. Zuojin Wan is an empirical formula of Zhu Danxi, one of the four great masters of the Jin-Yuan period, composed of Huanglian (Coptis) and Evodia in a 6:1 ratio. According to traditional TCM theory, Zuojin Wan clears liver fire, drains fire, downbears counterflow, and stops vomiting. It mainly treats liver-fire invading the stomach presenting as hypochondriac distending pain, vomiting with bitter mouth, and gastric emptiness with acid regurgitation. Today it is mainly used for acute and chronic gastritis and gastric ulcer due to liver-fire invading the stomach, and may also be used for gastric cancer, gallbladder cancer, and liver cancer presenting with the above symptoms.

Evodia's action on ascites is also recorded in ancient materia medica. The Rihuazi Bencao records it as treating "abdominal pain, kidney qi, beriberi, and edema." TCM has formulas using Evodia as the main ingredient for treating edema and abdominal distension.

For example, the Yifang Julei includes a Wuzhuyu Wan for "edema and abdominal distension": Wuzhuyu 4 liang (120 g), sweet Tinglizi (Descurainia) 2 liang (60 g, stir-fried), and Gansui (Euphorbia kansui) 1 liang (30 g, boiled in water). From a modern pharmacology perspective, all three herbs have diuretic and edema-reducing effects, so the formula can treat pleural effusion, ascites, or pelvic effusion.

The Baiyi Xuanfang also includes a "Wuzhu Pill" for "phlegm-rheum with upward counterflow, poor appetite, difficult urination, heavy head with dizziness, or headache and back coldness, vomiting of acidic fluid": white Fuling (Poria) and Wuzhuyu (soaked in water to remove foam) in equal parts. Grind into a fine powder, refine with honey into pills the size of a Wutongzi; take 30 pills each time. Here both Fuling and Evodia have diuretic and edema-reducing effects.

Evodia inhibits not only digestive tumors but also lung adenocarcinoma, breast cancer, leukemia, cervical cancer, melanoma, adenoid cystic carcinoma of the salivary gland, fibrosarcoma, prostate cancer, and colon cancer. It can inhibit pulmonary metastasis of cancer.

Evodia's analgesic action, recorded in ancient texts, has also been confirmed by modern pharmacology. Evodine has a marked central nervous system effect, expressed in analgesia and anti-anxiety. Evodine reduces the acetic-acid-induced ox-tendon response and the second phase of the formalin test, lowering pain sensitivity in inflamed paws of experimental animals.

Evodia has a strong anti-diarrheal effect; the famous anti-diarrheal TCM formula Sishen Wan contains Evodia. Evodia also works externally for diarrhea. The Chinese Journal of Integrated Traditional and Western Medicine published Wuzhuyu San, an external formula for acute, chronic, and persistent diarrhea in children: Wuzhuyu 2 g, Dingxiang (clove) 1.5 g, Muxiang (Aucklandia) 1.5 g, Rougui (cinnamon bark) 3 g, Cangzhu (Atractylodes) 3 g. Mix, crush, and sift. Take an appropriate amount, mix into a paste with vinegar, apply to the umbilicus, and seal with adhesive tape; change every two days. This external method can also treat diarrhea caused by chemotherapy or targeted therapy in cancer patients. For convenience, patients may buy empty plasters, mix the powder with vinegar, fill the plaster, and apply directly to the umbilicus.

In summary, Evodia helps address multiple problems in tumor patients and is a commonly used, multi-effect Chinese herb in oncology. But Evodia is somewhat toxic, so dosage must be controlled.