Wu Zhu Yu (Evodiae Fructus or Tetradii Fructus)

What Is Wu Zhu Yu

Wu Zhu Yu commonly known as Evodiae Fructus or Tetradii Fructus is the dried and nearly ripe fruit of Tetradium ruticarpum (A. Juss.), which is a deciduous shrub or tree belonging to the family Rutaceae. It is a relatively practical and common Chinese herbal medicine, which first appeared in <Shennong Ben Cao Jing> in the late Western Han Dynasty (around 100 BCE).

There are about 9 species of Tetradium, and they are mainly distributed in temperate to tropical regions of East Asia. Some of their species are medicinal plants.

Tetradium ruticarpum (A. Juss.) was previously and commonly known as Evodia rutaecarpa. This plant likes warm and humid environments. They often grow in sparse forests or bushes in mountains up to 1500 meters above sea level and are found mostly on sunny slopes. They are mainly distributed in China, Japan, Korea, Bhutan, Nepal, and Vietnam.

Tetradium ruticarpum

From August to November, when the fruits of Tetradium ruticarpum are nearly ripe, people cut off their fruiting branches, dry them in the sun or at low temperatures, remove their impurities such as branches, leaves, and fruit stalks, and use them directly, or moisten them with licorice soup, fry them until slightly dry, dry them, and make them into Zhi Wu Zhu Yu (Processed Evodiae Fructus).

Wu Zhu Yu contains evodiamine, 7β-hydroxyevodiamine, carboxyevodiamine, dihydrorutaecarpine, N14 -formyldihydrorutaecarpine, rutaecarpine, 7β-hydroxyrutaecarpine, rhetsinine, N,N-dimethy-5-methoxytryptamine, goshuyuamide-I, goshuyuamide-II, evodiamide, N-(2-methylaminobenzoyl)-tryptamine, β-carboline, 1,2,3,4-tetrahydro-1-oxo-β-carboline, acetonylevodiamine, evocarpine, dithdroevocarpine, DL-synephrine, higenamine, N-methylanthranylamide, sinephrine, synephrine, evoxanthine, berberine, limonin, 12α-hydroxylimonin, rutaevine, rutaevincacetate, graucin A, evodol, 12α-hydroxyevodol, obacunone, jangomolide, calodendrolide, evolimorutanin, quercetin, quercetin-3-O-β-D-glucopyranoside, quercetin-3-O-α-D-arabinopyranoside, hyperoside, epimedoside, catechin, cinchonain, isorhamnetin, diosmin, hesperidin, phenolic acids, volatile oils, amino acids, β-stigmasterol, β-sitosterol, daucosterol, syringin, coniferin, chrysophanol, emodin, physcion, and some trace elements.

Generally, the green and plump Wu Zhu Yu with a strong fragrance is preferred. Zhi Wu Zhu Yu is brown to dark brown.

According to the Chinese Pharmacopoeia, the medicinal nature of Wu Zhu Yu is relatively hot, with slight toxicity, and a pungent and bitter taste. It has a therapeutic effect on pathological changes in the liver, spleen, stomach, and kidney meridians.

In traditional Chinese medicine, it is often used to dispel cold to stop the pain, descend perverse rise of stomach-qi to stop vomiting, invigorate yang and relieve diarrhea, and treat headache, migraine, vomiting, abdominal pain, diarrhea, edema, beriberi, esophagitis, chronic gastritis, enteritis, gastric and duodenal ulcers, dyspepsia, angina pectoris, primary hypertension, functional uterine bleeding, dysmenorrhea, pelvic inflammatory disease, irregular menstruation, polycystic ovary syndrome, psoriasis, mumps, pinworms, scabies, eczema, and recurrent mouth ulcers.

There are more than 300 kinds of traditional Chinese medicine prescriptions containing it, such as Zuo Jin Wan, Si Shen Wan, and Shi Er Wen Jing Wan.

Benefits

  • Increasing pain threshold, prolonging the nociceptive time of mouse hot plate experiment, and reducing the number of writhing in mice induced by acetic acid.
  • Inhibiting the release of platelet granules induced by collagen, and mesenteric thrombosis caused by ferric chloride [1].
  • Reducing serum total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and hepatic cholesterol levels in hyperlipidemic rats and inhibiting the intestinal absorption of cholesterol [2].
  • Dispelling cold in the liver meridian, soothing liver qi for relieving qi stagnation, and treating Jueyin disease with headache, periumbilical colic, dysmenorrhea, beriberi, and edema caused by liver cold and qi stagnation.
  • Descending perverse rise of stomach-qi to stop vomiting, treating abdominal distension and pain, vomiting, and acid regurgitation caused by qi stagnation due to congealing cold.
  • Warming the spleen and reinforcing the kidney, invigorating yang, and treating diarrhea before dawn, loss of appetite, indigestion, and chronic diarrhea caused by insufficiency of both the spleen and the kidney.
  • Evodiamine can alleviate the hyperglycemia, hyperlipidemia, insulin resistance (IR), and pathological changes in the liver, pancreas, and kidneys in T2DM rats. Moreover, evodiamine can ameliorate the oxidative stress and decrease the serum levels of pro-inflammatory cytokines in T2DM model rats [3].
  • Evodiamine has inhibitory activity against colon cancer cells, gastric cancer cells, oral cancer cells, pancreatic cancer cells, liver cancer cells, lung cancer cells, nasopharyngeal cancer cells, leukemia T lymphocytes, glioblastoma cells, osteosarcoma cells, prostate cancer cells, bladder cancer cells, uroepithelial cell carcinoma, breast cancer cells, cervical cancer cells, ovarian cancer cells, and melanoma cells. It can exert a range of different physiological mechanisms, including inhibition of proliferation, induction of apoptosis, reduction of migration/invasion, and inhibition of metastasis [4].
  • Its polysaccharides have relatively stronger antioxidant activities, including ABTS, DPPH, OH, and O2−radical dot radicals scavenging activities, Fe2+ chelating ability, and α-glucosidase inhibitory effects [5].
  • Its ethanolic extracts have antibacterial activity against Helicobacter pylori and could be used in the treatment of gastric and duodenal ulcers [6].
  • Studies have found that evodiamine inhibited inflammation by inhibiting the phosphorylation of AKT, NF-κBp65, ERK1/2, p38, and JNK thus the LPS-induced mastitis was ameliorated [7].
  • Studies have found that evodiamine alleviated traumatic brain injury-induced neurological dysfunction, blood-brain barrier breakdown, histopathological changes in hematoxylin and eosin staining, and increased apoptosis. Importantly, evodiamine enhanced catalase (CAT) and superoxide dismutase (SOD) activities, and reduced reactive oxygen species (ROS) generation through PGK1 inhibition-induced activation of the NRF2/heme oxygenase-1 (HO-1) signaling in traumatic brain injury mice or H2O2-exposed PC12 cells [8].

Combinations

  • It can be used in combination with Sheng Jiang (Rhizoma Zingiberis Recens) and Ren Shen (Radix et Rhizoma Ginseng), etc. to treat Jueyin disease with vertex headache, vomiturition, slobbering, white fur, and slow pulse.
  • It can be used in combination with Xiao Hui Xiang (Fructus Foeniculi), Chuan Lian Zi (Fructus Meliae Toosendan), Mu Xiang (Radix Aucklandiae), etc. to treat periumbilical colic due to cold.
  • It can be used in combination with Gui Zhi (Ramulus Cinnamomi), Dang Gui (Radix Angelicae Sinensis), Chuan Xiong (Rhizoma Chuanxiong), etc. to treat dysmenorrhea caused by deficiency and cold in the Chong and Ren Meridians, and obstruction of blood stasis.
  • It can be used in combination with Mu Gua (Fructus Chaenomelis), Zi Su Ye (Perilla Leaf), Bing Lang (Semen Arecae), etc. to treat beriberi and edema caused by cold-dampness.
  • It can be used in combination with Xiao Hui Xiang (Fructus Foeniculi), Ding Xiang (Flos Caryophylli), Tan Xiang (Lignum Santali Albi), etc. to treat abdominal distension and pain caused by qi stagnation due to congealing cold.
  • It can be used in combination with Ban Xia (Pinellia Rhizome), Sheng Jiang (Rhizoma Zingiberis Recens), etc. to treat vomiting caused by pathogenic cold invading the interior, and failure of stomach qi to descend.
  • It can be combined with Huang Lian (Rhizoma Coptidis) to treat hypochondriac pain, bitter taste, vomiting, and acid regurgitation caused by liver depression transforming into the fire, and liver-stomach disharmony.
  • It can be used in combination with Rou Dou Kou (Semen Myristicae), Bu Gu Zhi (Fructus Psoraleae), and Wu Wei Zi (Fructus Schisandrae) to treat diarrhea before dawn, loss of appetite, indigestion, and chronic diarrhea caused by insufficiency of both the spleen and the kidney.

Side Effects

  • Wu Zhu Yu is considered a mildly toxic herbal medicine. Animal studies have confirmed that it causes liver damage in animals [9].
  • Overdose of it may cause toxic reactions such as severe abdominal pain, diarrhea, visual disturbance, delusion, hair loss, chest tightness, headache, dizziness, or morbilliform drug eruption.

Precautions and Warnings

  • The dosage of Wu Zhu Yu should be controlled between 2-5g.
  • It can be made into decoctions, pills, capsules, medicinal liquors, or grounds for external use.
  • People who are allergic to Wu Zhu Yu should not take it.
  • It should not be taken in excess or for long periods.
  • Patients with hyperactivity of fire due to yin deficiency should not take it.
  • Pregnant women should not take it.
  • Lactating women, children, and the elderly and infirm should be taken under the guidance of a physician.