Articles

Phellodendron

Plant Part Used

Bark, cortex

Active Constituents

Protoberberine alkaloids including berberine(1),(2),(3),(4) and palmatine.(5),(6)

Flavonoids such as limonoids including limonin, obakunone and nomilin,(7) and also indolopyridoquinazoline-type alkaloids 7,8-dihydroxyrutaecarpine and 7-hydroxyrutaecarpine.(8)

Flavone glycosides.(49)

Introduction

Editor's Note:While peer-reviewed scientific studies on this dietary supplement are lacking, many practitioners and individuals report observational and anectodal benefits from its use. Use of this dietary supplement is on the rise. For this reason, Intramedicine has provided this monograph using the information that is currently available. As more science-based research becomes available, this monograph will be updated to include that material.

 

For thousands of years the bark from the Phellodendron amurense tree has been used as an ingredient in herbal formulas in Chinese medicine. Traditionally these formulas have been used for gastroenteritis, abdominal pain and diarrhea. It has also been used as an antibacterial and anti-inflammatory. (9)

In addition, the bark of phellodendron was commonly used in traditional Chinese medicine for moisten dryness, purge fire and clear heat. (52) Also, this plant has potential in detoxifying and lowering blood sugar. (50)

The extractions of phellodendron have established important antimicrobial activity against a diversity of organisms together with bacteria, fungi, protozoa, viruses, helminthes and Chlamydia. Others, protoberberine alkaloids extract from phellodendron act as inhibition of smooth muscle contraction.(53)

Due to the extensive traditional use of phellodendron cortex in Chinese medicinal formulas, most of the information regarding phellodendron seems to stem from these herbal formulas. The use of multiple herbs in a formula make it difficult to deteremine which herb may be responsible for which pharmacological activity. The following information is a review of the research that has been published regarding the pharmacological activity of Phellodendron amurense, extracts made from it and several chemical constituents contained within it.

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

Phellodendron is generally used as an ingredient in numerous Chinese herbal formulas. No dosage information currently exists for phellodendron to be consumed alone.

Most Common Dosage

Please see Dosage Range.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

Not applicable

Uses

Frequently Reported Uses

  • Bacterial Infections
  • Topical Anti-inflammatory
  • Fungal Infections
  • Gastric Ulcers
Other Reported Uses
  • Diabetes
  • Immunosuppressive

Toxicities & Precautions

General

To date, phellodendron has not been associated with any adverse effects. An isoquinoline alkaloid known as berberine is contained within phellodendron extracts. Berberine is believed to be one of the constituents in phellodendron responsible for some pharmacological activity. Berberine has been associated with several adverse effects as noted below.

Health Conditions

Berberine possesses inotropic, chronotropic, antiarrhythmic and vasodilator properties. (10) Patients with various cardiovascular conditions including congestive heart failure, arrhythmias and hypertension should not use berberine containing products unless closely monitored by a health care professional.

Berberine has the ability to displace bilirubin, (11) , (12) therefore use berberine with caution in jaundice individuals, especially neonates.

Side Effects

A published review of berberine literature notes the following side effects: decrease in blood pressure, dyspnea, flu-like symptoms, gastrointestinal upset and possible cardiac damage. (13)

Pregnancy/ Breast Feeding

Due to berberine's ability to displace bilirubin, (14) , (15) as well as the traditional use of berberine as a uterine stimulant, (16) berberine and berberine containing products should not be used while pregnant or breast-feeding.

Age Limitations

Due to berberine's ability to displace bilirubin, (17) , (18) , berberine and berberine containing products should not be used in newborns, especially jaundiced newborns.

Pharmacology

A group of Japanese investigators isolated a fraction of phellodendri cortex extract that was berberine-free. This fraction has demonstrated some anit-inflammatory activity as well as anti-ulcer activity in rats. This extract significantly inhibited the formation of ulcers induced by ethanol, aspirin, stress and pylorus-ligation. Pylorus-ligated rats also demonstrated a reduction in gastric acid secretion when the fraction was administered via subcutaneous or intraduodenal routes. (19)

A study evaluated as many as 12 medicinal plants for their ability to inhibit the growth of candida species. A methanol extract of Phellodendron amurense caused significant inhibition of growth of Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis. Berberine and palmatine were identified as the predominant active ingredients in the extract. It is believed that one of the cellular targets for the antifungal activity of the protoberberines is 24-methyl transferase (24-SMT). In-vitro evaluation demonstrated that both berberine and palmatine inhibited the activity of 24-SMT in a non-competitive manner in the growth of the mycelial form of C. albicans and to lesser extent the yeast growth form of C. albicans. It is also suggested that palmatine inhibited chitin synthetase in both growth forms of C. albicans as well. (20)

Numerous plants traditionally used in East Asian medicine were evaluated for their topical anti-inflammatory activity. One of the plants evaluated in this study was Phellodendron amurense. Phellodendron demonstrated significant inhibition of the edema caused by TPA (12-O-tetradecanoylphorbol-13-acetate), oxalozone and arachidonic acid. No activity was noted against phospholipase A2. (21)

Animal studies have indicated that Phellodendri cortex and principles isolated from Phellodendri cortex can suppress local Graft v. Host (GvH) reactions as well as systemic allogeneic GvH reactions in mice. (22) , (23)

Phellodendron cortex water extract in a 1:1 ratio with Arlia cortex extract may help reduce the damaging effects of diabetes. Multiple animal studies have evaluated this herbal combination. In one of these studies, the damaging effect of oxidation and lipid peroxidation on the kidney in diabetic rats was evaluated. These extracts were able to exert an antioxidant effect by reducing the lipid peroxidation and protein carbonylation in the kidneys of these rats. (24) The same activity was noted in a similar rat study to be beneficial in reducing the oxidative damage that can occur on the lenses of diabetics. (25)

It has been reported that berberine has the ability in reducing body weight. The research in mice and rats indicated that berberine not reduced cell number but it reduced the adipocyte size of the body. It has been proved by metabolic gene expression measurements in adipose and muscle tissue which it is represented that berberine up regulated genes involved in energy expenditure and down regulated the expression of genes involved in lipogenesis. Besides, berberine also reduced accumulation of lipid in 3T3-L1 cells by increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes. (51)

Berberine is a well documented constituent found within phellodendron as well as several other medicinal plants, including goldenseal. (26) , (27) , (28) Berberine has well documented pharmacological activity that provide both beneficial effects as well as effects that may warrant concern.

Berberine has been shown to possess antimicrobial activity. The antibacterial activity berberine may benefit individuals suffering from diarrhea caused by Vibrio cholerae and Escherichia coli. (29) , (30) , (31) Berberine possesses activity against fungi, especially various species of Candida, (32) chlamydia trachomatis (33) and has demonstrated activity against protozoans as well. (34)

Berberine possesses cardiovascular effects. A review of the medical literature has indicated positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. (35) These properities may provide some benefit in patients with congestive heart failure (CHF) (36) or in patients with arrhythmias. (37)

Berberine in numerous ways has demonstrated activity against the development and the progression of various types of cancer. Berberine has demonstrated inhibition of DNA-synthesis in activated lymphocytes (38) and dose-dependent inhibition of N-acetyltransferase (NAT) activity and 2-aminofluorene (AF)-DNA adduct formation in human leukemia cells. (39) Via down-regulation of nucleophosmin/B23 and telomerase activity, berberine induces apoptosis in human leukemia cells. (40) NAT has also been inhibited in a dose-dependent manner by berberine in human colon tumor cell lines. (41) The cyclooxygenase-2 (COX-2) enzyme is expressed in colon cancer cells and plays a role in colon tumor formation. Berberine has demonstrated dose- and time-dependent inhibition of this enzyme in colon cancer cell lines. (42) Studies in rats and mice have demonstrated berberine's ability to inhibit 20-methylcholanthrene induced carcinogenesis (43) as well as protect against cyclophosphamide-induced cystitis with pretreatment of berberine. (44) Berberine has also been noted to have anti-tumor promoting activity. A laboratory study involving human hepatoma cells was completed to evaluate the effect of berberine on a transcription factor, activator protein 1 (AP-1). AP-1 plays a role in inflammation and carcinogenesis and was inhibited in a dose and time dependent manner by berberine. (45)

A study done in rabbits found a dose-dependent inhibition of collagen-, ADP-, and arachidonic acid-induced Thromboxane A2 release from platelets by berberine, suggesting that berberine inhibits AA release from cell membrane phospholipids. (46) Utilizing the effects of berberine on collagen, ADP and arachidonic acid another study in rats with 24 hour reversible middle cerebral artery occlusion, berberine inhibited platelet aggregation and platelet adhesiveness. (47)

Recently, the laboratory animal study has elucidated that nexrutine extraction from phellodendron has the ability to prevent prostate cancer. The result reported that nexrutine capable to protect transgenic adenocarcinoma of mouse prostate (TRAMP) from emerging proliferation of prostate cancer. (49)

Another animal study has reported that phellodendron bark has effectiveness in treating urinary tract disorders. The phellodendron mechanism has inhibited contractility of prostate gland and therefore it is useful in the treatment of urological disorders such as benign prostatic hyperplasia (BPH) that has caused by prostatic urethral obstruction. (52)

References

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  2. View Abstract: Wang YM, Zhao LB, Lin SL, Dong SS, An DK. Determination of berberine and palmatine in cortex phellodendron and Chinese patent medicines by HPLC. Yao Hsueh Hsueh Pao. 1989;24(4):275-9.
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  5. View Abstract: Miyake M, Inaba N, Ayano S, Ozaki Y, Maeda H, Ifuku Y, et al. Limonoids in Phellodendron amurense (Kihada). Yakugaku Zasshi. May1992;112(5):343-7.
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  25. View Abstract: Lee Y, Kim H, Choi HS, Kang BH, Han YB, Kim SJ. Effects of water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex on polyol pathway and oxidative damage in lenses of diabetic rats. Phytother Res. Nov1999;13(7):555-60.
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  28. View Abstract: Abourashed EA, Khan IA. High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal. J Pharm Sci. Jul2001;90(7):817-822.
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  47. View Abstract: Wu JF, Liu TP. Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion. Yao Xue Xue Bao. 1995;30(2):98-102.
  48. Garcia G.E., et al. Akt- and CREB-Mediated Prostate Cancer Cell Proliferation Inhibition by Nexrutine, a Phellodendron amurense Extract. Neoplasia. June2006;8(6): 523–533.
  49. Kumar A.P., et al. Akt/CREB/Cyclin D1 network: a novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate (TRAMP) model mediated by Nexrutine®, a Phellodendron amurense bark extract. Clin Cancer Res. May2007;13(9): 2784–2794
  50. Azad M.A.K., et al. Plant regeneration through somatic embryogenesis of a medicinal plant, Phellodendron amurense Rupr. In Vitro Cellular & Developmental Biology – Plant. August 2009;4(45) :441–449.
  51. Oben J., et al. Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study. Nutrition Journal. Aug2009;8(38).
  52. Xu Y., Ventura S. Extracts of bark from the traditional Chinese herb Phellodendron amurense inhibit contractility of the isolated rat prostate gland. Journal of Ethnopharmacology. Sep2009;127:196–199.
  53. Li C.Y., et al. A rapid and simple determination of protoberberine alkaloids in cortex phellodendri by H NMR and its application for quality control of commercial traditional Chinese medicine prescriptions. Journal of Pharmaceutical and Biomedical Analysis. 2006;40:173–178.