Wu Zhu Yu

Evodiae Fructus; Evodia rutaecarpa

Chemical Constituents

Alkaloids including evodiamine, rutaecarpine evocarpin (1), 1-methyl-2-[(4Z,7Z)-4,7-tridecadienyl]-4(1H)-quinolone and 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolone, synephrine. [2][3][4]

Dosage

Dried fruit: 1.5 – 12gm daily as a decoction. Place dried fruit in water and boil 5-10 minutes. Strain and drink up to 3 times daily.

Pharmacology

Pre-clinical

Traditional Use

Evodia rutaecarpa is acrid or pungent, hot and bitter, downward directing and drying. [11] It works through the liver, spleen and stomach channels and is used to dispel cold, reduce pain, reduce nausea and limiting diarrhea. [12]

General 

Anti-inflammatory activity: 

Evodiamine and rutaecarpine, alkaloids found in E. rutaecarpa have been reported to have anti-inflammatory activity. [13] The mechanisms include inhibition of prostaglandin E2 synthesis, cyclooxygenase-2 (COX-2) inhibition, inhibition of iNOS expression and NF-kappaB activation. [14][15] Another laboratory study found that evodiamine inhibited NADPH oxidase-dependent reactive oxygen species and/or lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible NO synthetase (iNOS) expression in microglial cells. [16] 

An in vitro study found that evodiamine and rutaecarpine may be effective for IgE-induced allergic diseases such as atopic dermatitis and rhinitis. [17] The two constituents inhibited TNF-alpha and IL-4 protein expression in cells induced by IgE-antigen complex, further supporting the use of anti-inflammatory compounds found in evodia. 

Cytotoxic activity: 

Evodiamine, an alkaloid found in E. rutaecarpa, exhibits antitumor activities against the human tumor cells, including multidrug-resistant tumor cells. [18] A proposed mechanism is evodiamine’s ability to inhibit cell growth and induce apoptosis. [19][20] 

Thermogenic activity: 

In laboratory animal studies, evodiamine has been reported to have vanilloid receptor agonistic activities comparable to capsaicin, increasing thermogenesis ( heat loss and heat production) and dissipating food energy, preventing the accumulation of perivisceral fat and the resulting body weight increase. [21] 

Other activity: 

Laboratory animal studies have found that water extracts of E. rutaecarpa may be beneficial in gastrointestinal ulcers, supporting the traditional use of eviodia for digestive problems. [22] The gastroprotective mechanisms maybe due to the strengthening action on gastric mucosal lining and the promotion of nitric oxide synthesis in local gastric mucosa.

Clinical

No documentation.

Interaction and Depletions

Interaction with other Herbs

No documentation.

Interaction with Drugs

Wu Zhu Yu may have antiplatelet activity, so caution is advised in those with bleeding disorders. [5] 

Wu Zhu Yu contains small amounts of synephrine, so use with caution in individuals with heart conditions, such as hypertension or arrhythmias. [6] 

Based on pharmacology, use with caution in individuals taking ACE inhibitors, individuals taking MAO inhibitors due to the potential for MAO-B inhibition, individuals take cardiac medications, including antihypertensives and antiarrhythmics. [7][8][9] 

Use with caution if taking theophylline. Theophylline levels were significantly lowered when using Evodia extracts in laboratory animals. [10] Use with caution if taking antiplatelet drugs or anticoagulants, such as aspirin or warfarin. [5] 

Precautions and Contraindications

Side effects

Discontinue if allergy occurs.

Pregnancy

Do not use in pregnancy or lactation.

Age limitation

No documentation.

Adverse reaction

The oral LD50 of an extract of Wu Zhu Yu in mice was measured at more than 10.0 g/kg(-1). No genotoxicity was demonstrated. [1] 

References

  1. X.W. Yang.Toxicological assessment on safety of water and 70% ethanolic extracts of nearly ripe fruit of Evodia rutaecarpa. Zhongguo Zhong Yao Za Zhi. Jun2008;33(11):1317-1321.
  2. Y. Zhao, X. Zhou, H.G. Chen. Determination of dehydroevodiamine in Evodia rutaecarpa (Juss.) Benth by high performance liquid chromatography and classification of the samples by using hierarchical clustering analysis. Fitoterapia. Oct2009;80(7):415-420.
  3. X. Gong, X. Zhou, Z. Cai, J. Zhang, W. Zhou. Studies on chemical constituents of Evodia rutaecarpa. Zhongguo Zhong Yao Za Zhi. Jan2009;34(2):177-179.
  4. H.C. Ko, K.T. Chen, C.F. Chen. Chemical and biological comparisons on Evodia with two related species of different locations and conditions. J Ethnopharmacol. 24Nov2006;108(2):257-263.
  5. J.R. Sheu, W.C. Hung, Y.M. Lee, M.H. Yen. Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa. Eur J Pharmacol. 30Dec1996;318(2-3):469-475.
  6. S. Ihara, H. Shimoda, Y. Akiho. Application of Capillary Electrophoresis to Estimate Synephrine Levels in Evodia Fruit. Nat Med. 2003.57(5): 110-113.
  7. H.S. Lee HS, Oh WK, Choi HC, et al. Inhibition of angiotensin II receptor binding by quinolone alkaloids from Evodia ritaecarpa. Phytotherapy Research. 1998;12(3):212-214.
  8. X.H. Han, S.S. Hong, D. Lee. Quinolone alkaloids from evodiae fructus and their inhibitory effects on monoamine oxidase. Arch Pharm Res. Apr2007;30(4):397-401.
  9. F. Pellati, S. Benvenuti, F. Yoshizaki, M. Melegari. Development and validation of HPLC methods for the analysis of phenethylamine and indoloquinazoline alkaloids in Evodia species. J Sep Sci. Mar2006;29(5):641-649.
  10. W.C. Jan, L.C. Lin, F.C. Chieh, T.H. Tsai. Herb-drug interaction of Evodia rutaecarpa extract on the pharmacokinetics of theophylline in rats. J Ethnopharmacol. 1Dec2005;102(3):440-445.
  11. D. Bensky, S. Clavey, E. Stoger, A. Gamble. Chinese Herbal Medicine Materia Medica, 3rd Edition. Seattle WA:Eastland Press; 2004.30.
  12. Z. You-Ping. Chinese Matria Medica: Chemistry, Pharmacology and Applications. Florida:CRC Press;1998 352-353.
  13. Y.N. Liu, S.L. Pan, C.H. Liao. Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia-inducible factor 1alpha accumulation in RAW264.7. Shock. Sep2009;32(3):263-269.
  14. Y.H. Choi, E.M. Shin, Y.S. Kim, X.F. Cai, J.J. Lee, H.P. Kim. Anti-inflammatory principles from the fruits of Evodia rutaecarpa and their cellular action mechanisms. Arch Pharm Res. Apr2006;29(4):293-297.
  15. T.C. Moon, M. Murakami, I. Kudo. A new class of COX-2 inhibitor, rutaecarpine from Evodia rutaecarpa. Inflamm Res. Dec1999;48(12):621-625.
  16. H.C. Ko, Y.H. Wang, K.T. Liou. Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells. Eur J Pharmacol. 26Jan 2007;555(2-3):211-217.
  17. Y.W. Shin, E.A. Bae, X.F. Cai, J.J. Lee, D.H. Kim. In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and its constituents. Biol Pharm Bull. Jan2007;30(1):197-199.
  18. T.J. Lee, E.J. Kim, S. Kim. Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells. Mol Cancer Ther. Sep2006;5(9):2398-2407.
  19. Z.G. Yang, A.Q. Chen, B. Liu. Antiproliferation and apoptosis induced by evodiamine in human colorectal carcinoma cells (COLO-205). Chem Biodivers. Jun2009;6(6):924-933.
  20. J. Jiang, C. Hu. Evodiamine: a novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules. 18May2009 ;14(5):1852-1859.
  21. Y. Kobayashi, Y. Nakano, M. Kizaki, K. Hoshikuma, Y. Yokoo, T. Kamiya. Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med. Oct2001;67(7):628-633.
  22. X. Yu, D.Z. Wu. Protective effects of Evodia rutaecarpa water extract on ethanol-induced rat gastric lesions. Zhongguo Zhong Yao Za Zhi. Nov2006;31(21):1801-1803.