Huáng bǎi

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Huáng bǎi (黄栢 or 黃栢, literally "yellow fir") or huáng bò (黄檗) is one of the fifty fundamental herbs of traditional Chinese medicine. Known also as Cortex Phellodendri, it is the bark of one of two species of Phellodendron tree: Phellodendron amurense or Phellodendron chinense.

Huáng bǎi
Alternate names：huáng bò, yuán bò
Source
Tree bark of the Rutaceae plants Phellodendron chinense Schneid. or Phellodendron amurense
Medicinal activity
Taste bitter, cold
Tropism kidney, urinary bladder, large intestine
Efficacy clears and dries damp heat? (清热燥湿), flushes away fire and removes steam? (泻火除蒸), binds up poison and cures sores? (解毒疗疮)
Uses
Indications Moist heat (下焦湿热症状)
Internal use Pills or powder
External use As suitable
Recommendations
Counterindications Spleen weakness
Manufacture
Harvesting Tree bark collected March to May
Storage Dry and ventilated place
Processing Salt, alcohol, charcoal? methods
Chinese medicine chemical ingredient
berberine
A fully mature (150 yr) Phellodendron amurense tree. Huáng bǎi is typically harvested from trees 10 years old.
Phellodendron amurense cross-section. For a younger specimen see

Cultivation

For Phellodendron amurense (关黄柏, i.e. "highland Phellodendron") one of the major producing areas is Taoshan District of Heilongjiang province, though other regions of Heilongjiang, Jilin, Liaoning and Inner Mongolia may also be suitable.[1] These provinces are in the far northeast of China, near the Heilong Jiang river, known in Russian as the Аму́р (Amur River), and Phellodendron amurense is commonly known as the Amur cork tree.

Phellodendron chinense (川黄柏, i.e. "lowland Phellodendron") producing areas include Sichuan, Hubei, Guizhou, Yunnan, and Guangxi.[2]

Preparation

Bark is collected during Qingming (Pure Brightness), the fifth solar term (April 4–20). It is sun-dried and cut into slices. The bark may be used raw or fried with salt. Typical dosage is 3-10 grams.[3] A variety of methods of water and ethanol extraction may have differing activities (see below) and methods such as "semi-bionic extraction" have been investigated to improve yields.[4] Some pharmacological activities of the bark can be standardized by analyzing the level of berberine using a monoclonal antibody,[5] thin-layer chromatography,[6][7] HPLC,[8] potentiometry,[9] or acidic potassium permanganate chemiluminescence.[10] There are quantitative differences between the two species of Cortex Phellodendri (P. amurense and chinense) and it has been suggested that they should be used as separate resources in the clinic.[11] An analysis of 31 commercial samples in 1993 found that the total level of five alkaloids in samples of P. wilsonii and P. amurense var. sachalinense was 4.1% (mostly berberine), while the level in P. amurense and Ph. chinense was 1.5%.[12]

The levels of four harmful trace heavy metals (arsenic, cadmium, mercury, and thallium) in P. chinense for export are limited by the Pharmacopoeia of the People's Republic of China and the Green Trade Standard for Importing and Exporting Medicinal Plant and Preparation.[13]

History

The earliest known report of this medicine is in the Shen nong ben cao jing[3]

Traditional attributes

The bark is categorized in a traditional Chinese medicine counterpart of humorism, Wu Xing, as bitter and cold, affecting the kidney, urinary bladder and large intestine meridians. Is said "to clear heat and dry dampness", and "to reduce fire and release toxins".[3]

Physiological effects

A wide range of primary scientific publications have been made about the activities of extracts of Phellodendron bark, primarily from the People's Republic of China. These should be evaluated cautiously, as many of them represent small studies, with little confirmation, and occasionally are subject to conflict of interest, but they are what is available.

In mice with hyperuricemia, Phellodendron amurense (whether raw or processed with salt) reduced blood uric acid levels by inhibiting xanthine oxidase activity.[14]

In vitro studies found that the extract reduced neuronal cell death (apoptosis) in a tissue culture line treated with a strong toxin (MPTP).[15] By contrast, it was identified as a possible inducer of apoptosis in HL-60 cells.[16]

Various preparations of the bark showed antioxidant activities, with an 80% ethanol extract of the bark stir-fried with yellow alcohol having the largest effect.[17]

Phellodendron amurense[18] and Coptis chinensis[19] were identified from among 297 Chinese medicines as herbs that reduce activation of NF-κB by a liver cell line in response to acetaldehyde, a breakdown product of ethanol associated with cirrhosis. NF-κB is part of an inflammatory process, and it is believed that berberine, a component of the two herbs, is responsible for the effect.[20] Phellodendron amurense also inhibited proinflammatory iNOS and TNF-alpha activity in a glial cell line[21] and has topical anti-inflammatory activity.[22] Phellodendron wilsonii was found to have a hepatoprotective activity in carbon tetrachloride treated rats.[23]

Ethanol extracts, but not water extracts, of huáng bǎi appeared to exert antidiarrheal activity by attenuating ion transport by intestinal epithelium.[24]

Medicinal extracts of the bark reduced the rate of growth of Candida, which has been ascribed to berberine and palmatine content.[25] They have also been investigated for use against Mycoplasma hominis,[26] Propionibacterium acnes,[27] and Helicobacter pylori.[28] A bark extract was reported to reduce formation of stomach ulcers in mice under several stresses, due to cytoprotection and reduced secretion of stomach acid.[29] The cytoprotective effect against ulcers is abolished by pretreatment with N-ethylmaleimide, suggesting that sulfhydryl compounds are involved.[30]

A methanol extract (100–400 mg/kg) was found to protect against airway inflammation in response to lipopolysaccharide treatment of mice.[31]

The extract (379 mg/kg) was found to reduce blood glucose levels and slow the development of diabetic nephropathy in mice treated with streptozocin to induce diabetes.[32] Similar effects have been attributed to berberine.[33][34]

Extracts of the bark have been reported to reduce contractions of smooth muscle of isolated rat prostate glands.[18] Certain polysaccharide fractions from Phellodendron chinense were reported to increase T cell activity and reduce cell replication of tumors in mice.[35] A group studying Nexrutine, a brand of fractionated extract, found that it reduced the rate of replication of prostate tumor cells.[36][37] Tests of Nexrutine (300–600 mg/kg) in a mouse strain designed to develop prostate cancer found a dramatic reduction in palpable tumors.[38] Another brand, Prostant, has been used for chronic prostatitis[39]

Phellodendrine and magnoflorine from the bark showed an immunosuppressive effect on local graft-versus-host reactions in mice, but phellodendrine does not affect antibody production in mice to SRBC.[40][41]

Combination therapies

In combination with Citrus sinensis extract, it reduced pain and inflammatory markers in arthritis patients, with apparent benefits on weight loss and cardiovascular health.[42][43]

Traditional Chinese medicines containing Huáng bǎi include:

  • Sān miáo wán
  • Ankun Zanyu Wan (按坤赞育丸)
  • Baidai Wan (白带丸)
  • Biyan Pian (鼻炎片)
  • Dabuyin Wan
  • Ermiao Wan (二妙丸)[44][45]
  • Fufang Caoshanhu Hanpian (复方草珊瑚含片)
  • Guilin Xiguashuang (桂林西瓜霜)
  • Gujing Wan (固经丸)
  • Heche Dazao Wan (河车大造丸)
  • Huanglian Yanggan Wan (黄连羊肝丸)
  • Jianbu Wan (健步丸)
  • Zhibai Dihuang Wan
  • Qingfei Yihuo Wan
  • Huanglian Shangqing Wan
  • Huanglian Jiedutang[46][47]
  • Pentaherbs formula[48]
  • Shenbaiye[49]
  • Oren-gedoku-to (described by a Japanese source as a traditional Chinese medicine for stomach ulcer)[50]

Korean medicines include:

Cortex Phellodendri, known in Japanese as Ōbaku (黄檗) is also among the Kampo herb list of traditional Japanese medicine. The 1249 treatise Pí Wèi Lùn, known in Japanese as the Hi-i-ron, notably recommended it in combination with sweet Qi-tonics (Hoki-yaku) such as Ginseng and Atractylodis Macrocephalae Rhizome, but these formulations are less prominent in the Nei Wai Shang Bian Huo Lun.[53] Use of the root (Radix Phellodendri) was described in the 1735 Sambutsu-cho.[54]

Use of the herb has been unknown in European medicine.[55]

Biochemical analysis

Small molecules found in the bark include:

References

  1. ↑ Suo, FM; Chen, SL; Zhang, Z; Xie, CX (2008). "Ecological evaluation of suitable area for production of Phellodendron amurense based on TCMGIS- I". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 33 (13): 1536–9. PMID 18837308. 
  2. ↑ 《中国药物志》 北京：科学出版社，1997，43(2) 99~103
  3. ↑ 3.0 3.1 3.2 "Traditional Chinese Medicine basics". 
  4. ↑ Zhang, X; Zhang, Z; Xu, X; Wang, Y (1999). "Comparison of semi-bionic extraction and water extraction in extraction of chemical constituents from processed cortex Phellodendri". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 24 (10): 600–2, 638. PMID 12205956. 
  5. ↑ Kim, JS; Tanaka, H; Shoyama, Y (2004). "Immunoquantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines". The Analyst 129 (1): 87–91. doi:10.1039/b311304c. PMID 14737589. 
  6. ↑ Xu, PS; Tan, GS; Li, XZ (2000). "A study of quality standards for fuyanke granule". Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 25 (5): 502–4. PMID 12212134. 
  7. ↑ Zhou, H; Gu, Y (1995). "Determination of berberine in Phellodendron chinense Schneid and its processed products by TLC (thin layer chromatography) densitometry". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 20 (7): 405–7, 447. PMID 7576137. 
  8. ↑ Wang, YM; Zhao, LB; Lin, SL; Dong, SS; An, DK (1989). "Determination of berberine and palmatine in cortex phellodendron and Chinese patent medicines by HPLC". Yao xue xue bao = Acta pharmaceutica Sinica 24 (4): 275–9. PMID 2816389. 
  9. ↑ Liu, WZ; Peng, WB; Yang, CH (1991). "Berberine-electrochemical detector for the determination of berberine-type alkaloids in various Chinese patent medicines by flow injection analysis". Yao xue xue bao = Acta pharmaceutica Sinica 26 (4): 315–9. PMID 1957679. 
  10. ↑ Xu, X; Lin, Q; He, X; Fu, F; Chen, G (2010). "Determination of protoberberine alkaloids in medicinal plants based on acidic potassium permanganate chemiluminescence system". Luminescence : the journal of biological and chemical luminescence 25 (5): 403–8. doi:10.1002/bio.1169. PMID 19743526. 
  11. ↑ Hu, YM; Su, GH; Sze, SC; Ye, W; Tong, Y (2010). "Quality assessment of Cortex Phellodendri by high-performance liquid chromatography coupled with electrospray ionization mass spectrometry". Biomedical chromatography : BMC 24 (4): 438–53. doi:10.1002/bmc.1311. PMID 19711298. 
  12. ↑ Liu, YM; Sheu, SJ; Chiou, SH; Chang, HC; Chen, YP (1993). "A comparative study on commercial samples of phellodendri cortex". Planta medica 59 (6): 557–61. doi:10.1055/s-2006-959761. PMID 17230366. 
  13. ↑ Kou, XM; Xu, M; Gu, YZ (2007). "Determination of trace heavy metal elements in cortex Phellodendron chinense by ICP-MS after microwave-assisted digestion". Guang pu xue yu guang pu fen xi = Guang pu 27 (6): 1197–200. PMID 17763791. 
  14. ↑ Yang, C; Zhu, JX; Wang, Y; Wen, YL; Kong, LD (2005). "Effects of processing Phellodendron amurense with salt on anti-gout". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 30 (2): 145–8. PMID 15714822. 
  15. ↑ Jung, HW; Jin, GZ; Kim, SY; Kim, YS; Park, YK (2009). "Neuroprotective effect of methanol extract of Phellodendri Cortex against 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis in PC-12 cells". Cell biology international 33 (9): 957–63. doi:10.1016/j.cellbi.2009.06.006. PMID 19524685. 
  16. ↑ Nishida, S; Kikuichi, S; Yoshioka, S; Tsubaki, M; Fujii, Y; Matsuda, H; Kubo, M; Irimajiri, K (2003). "Induction of apoptosis in HL-60 cells treated with medicinal herbs". The American journal of Chinese medicine 31 (4): 551–62. doi:10.1142/S0192415X03001211. PMID 14587878. 
  17. ↑ Kong, LD; Yang, C (2001). "Effects of different processing products of Cortex Phellodendri on scavenging oxygen free radicals and anti-lipid peroxidation". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 26 (4): 245–8. PMID 12525047. 
  18. ↑ 18.0 18.1 Xu, Y; Ventura, S (2010). "Extracts of bark from the traditional Chinese herb Phellodendron amurense inhibit contractility of the isolated rat prostate gland". Journal of Ethnopharmacology 127 (1): 196–9. doi:10.1016/j.jep.2009.09.047. PMID 19799978. 
  19. ↑ http://www.wipo.int/pctdb/en/wo.jsp?wo=2001045725
  20. ↑ Hsiang, CY; Wu, SL; Cheng, SE; Ho, TY (2005). "Acetaldehyde-induced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factor-kappaB signaling pathway in HepG2 cells". Journal of biomedical science 12 (5): 791–801. doi:10.1007/s11373-005-9003-4. PMID 16132116. 
  21. ↑ Park, YK; Chung, YS; Kim, YS; Kwon, OY; Joh, TH (2007). "Inhibition of gene expression and production of iNOS and TNF-alpha in LPS-stimulated microglia by methanol extract of Phellodendri cortex". International immunopharmacology 7 (7): 955–62. doi:10.1016/j.intimp.2006.03.018. PMID 17499198. 
  22. ↑ Cuéllar, MJ; Giner, RM; Recio, MC; Máñez, S; Ríos, JL (2001). "Topical anti-inflammatory activity of some Asian medicinal plants used in dermatological disorders". Fitoterapia 72 (3): 221–9. doi:10.1016/S0367-326X(00)00305-1. PMID 11295297. 
  23. ↑ Chiu, HF; Lin, CC; Yang, CC; Yang, F (1988). "The pharmacological and pathological studies on several hepatic protective crude drugs from Taiwan (I)". The American journal of Chinese medicine 16 (3–4): 127–37. doi:10.1142/S0192415X88000194. PMID 3245533. 
  24. ↑ Tsai, JC; Tsai, S; Chang, WC (2004). "Comparison of two Chinese medical herbs, Huangbai and Qianniuzi, on influence of short circuit current across the rat intestinal epithelia". Journal of Ethnopharmacology 93 (1): 21–5. doi:10.1016/j.jep.2004.02.024. PMID 15182899. 
  25. ↑ Park, KS; Kang, KC; Kim, JH; Adams, DJ; Johng, TN; Paik, YK (1999). "Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans". Journal of antimicrobial chemotherapy 43 (5): 667–74. doi:10.1093/jac/43.5.667. PMID 10382888. 
  26. ↑ Che, YM; Mao, SH; Jiao, WL; Fu, ZY (2005). "Susceptibilities of Mycoplasma hominis to herbs". The American journal of Chinese medicine 33 (2): 191–6. doi:10.1142/S0192415X05002862. PMID 15974478. 
  27. ↑ Higaki, S; Hasegawa, Y; Morohashi, M; Takayoshi, Y (1995). "The correlation of Kampo formulations and their ingredients on anti-bacterial activities against Propionibacterium acnes". The Journal of dermatology 22 (1): 4–9. PMID 7897023. 
  28. ↑ Du, P; Zhu, S; Lü, P (2001). "Antibacterial activity of 20 kinds of Chinese medicinal materials for Helicobacter pylori in vitro". Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 24 (3): 188–9. PMID 12587175. 
  29. ↑ Uchiyama, T; Kamikawa, H; Ogita, Z (1989). "Anti-ulcer effect of extract from phellodendri cortex". Yakugaku Zasshi 109 (9): 672–6. PMID 2607417. 
  30. ↑ Takase, H; Inoue, O; Saito, Y; Yumioka, E; Suzuki, A (1991). "Roles of sulfhydryl compounds in the gastric mucosal protection of the herb drugs composing oren-gedoku-to (a traditional herbal medicine)". Japanese journal of pharmacology 56 (4): 433–9. doi:10.1254/jjp.56.433. PMID 1660547. 
  31. ↑ Mao, YF; Li, YQ; Zong, L; You, XM; Lin, FQ; Jiang, L (2010). "Methanol extract of Phellodendri cortex alleviates lipopolysaccharide-induced acute airway inflammation in mice". Immunopharmacology and immunotoxicology 32 (1): 110–5. doi:10.3109/08923970903193325. PMID 19811108. 
  32. ↑ Kim, HJ; Kong, MK; Kim, YC (2008). "Beneficial effects of Phellodendri Cortex extract on hyperglycemia and diabetic nephropathy in streptozotocin-induced diabetic rats". BMB reports 41 (10): 710–5. doi:10.5483/BMBRep.2008.41.10.710. PMID 18959817. 
  33. ↑ Liu, WH; Hei, ZQ; Nie, H; Tang, FT; Huang, HQ; Li, XJ; Deng, YH; Chen, SR et al. (2008). "Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase". Chinese medical journal 121 (8): 706–12. PMID 18701023. 
  34. ↑ Liu, W; Liu, P; Tao, S; Deng, Y; Li, X; Lan, T; Zhang, X; Guo, F et al. (2008). "Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose". Archives of biochemistry and biophysics 475 (2): 128–34. doi:10.1016/j.abb.2008.04.022. PMID 18471986. 
  35. ↑ Park, SD; Lai, YS; Kim, CH (2004). "Immunopontentiating and antitumor activities of the purified polysaccharides from Phellodendron chinese SCHNEID". Life Sciences 75 (22): 2621–32. doi:10.1016/j.lfs.2004.03.036. PMID 15369698. 
  36. ↑ Muralimanoharan, SB; Kunnumakkara, AB; Shylesh, B; Kulkarni, KH; Haiyan, X; Ming, H; Aggarwal, BB; Rita, G et al. (2009). "Butanol Fraction Containing Berberine or Related Compound From Nexrutine® Inhibits NFκB Signaling and Induces Apoptosis in Prostate Cancer Cells". The Prostate 69 (5): 494–504. doi:10.1002/pros.20899. PMC 2674392. PMID 19107816. 
  37. ↑ Gretchen E Garcia et al. (June 2006). "Akt- and CREB-Mediated Prostate Cancer Cell Proliferation Inhibition by Nexrutine, a Phellodendron amurense Extract". Neoplasia 8 (6): 523–533. doi:10.1593/neo.05745. PMC 1601469. PMID 16820098. 
  38. ↑ Addanki P Kumar et al. (2007-05-01). "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. 13 (9): 2784–2794. doi:10.1158/1078-0432.CCR-06-2974. PMC 1948816. PMID 17473212. 
  39. ↑ Xu, G; Zhang, YF; Ding, Q (2003). "Efficacy of Prostant on chronic prostatitis in 119 patients". Acta pharmacologica Sinica 24 (6): 615–8. PMID 12791192. 
  40. ↑ Mori, H; Fuchigami, M; Inoue, N; Nagai, H; Koda, A; Nishioka, I; Meguro, K (1995). "Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responses". Planta medica 61 (1): 45–9. doi:10.1055/s-2006-957997. PMID 7700991. 
  41. ↑ Mori, H; Fuchigami, M; Inoue, N; Nagai, H; Koda, A; Nishioka, I (1994). "Principle of the bark of Phellodendron amurense to suppress the cellular immune response". Planta medica 60 (5): 445–9. doi:10.1055/s-2006-959529. PMID 7997475. 
  42. ↑ Oben, J; Enonchong, E; Kothari, S; Chambliss, W; Garrison, R; Dolnick, D (2009). "Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study". Nutrition journal 8: 38. doi:10.1186/1475-2891-8-38. PMC 2739863. PMID 19682376. 
  43. ↑ Oben, J; Enonchong, E; Kothari, S; Chambliss, W; Garrison, R; Dolnick, D (2008). "Phellodendron and Citrus extracts benefit cardiovascular health in osteoarthritis patients: a double-blind, placebo-controlled pilot study". Nutrition journal 7: 16. doi:10.1186/1475-2891-7-16. PMC 2409365. PMID 18492265. 
  44. ↑ Kong, L; Yang, Chen; Ge, Fei; Wang, Hai Dong; Guo, Yu Song (2004). "A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice". Journal of Ethnopharmacology 93 (2–3): 325–330. doi:10.1016/j.jep.2004.04.008. PMID 15234772. 
  45. ↑ Carro, M.D.; Falkenstein, E.; Radke, W.J.; Klandorf, H. (2010). "Effects of allopurinol on uric acid concentrations, xanthine oxidoreductase activity and oxidative stress in broiler chickens". Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 151: 12–17. doi:10.1016/j.cbpc.2009.07.010. 
  46. ↑ Ma, Z; Yang, X; Zhong, G (2009). "A new flavonoid glucoside from Huanglianjiedutang decoction". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 34 (9): 1097–100. PMID 19685742. 
  47. ↑ Zhang, DM; He, ZW; Liu, XD; Li, Y; Xie, L; Wang, GJ; Liu, L (2007). "In-vivo and in-vitro studies on the effect of Huang-Lian-Jie-Du-Tang on nimodipine transport across rat blood–brain barrier". The Journal of pharmacy and pharmacology 59 (12): 1733–8. doi:10.1211/jpp.59.12.0017. PMID 18053337. 
  48. ↑ Chan, BC; Hon, KL; Leung, PC; Sam, SW; Fung, KP; Lee, MY; Lau, HY (2008). "Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells". Journal of Ethnopharmacology 120 (1): 85–91. doi:10.1016/j.jep.2008.07.034. PMID 18725279. 
  49. ↑ Wu, C; Zhou, Z; He, Y (1998). "Identification and determination of Shenbaiye". Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao / [bian ji zhe, Hua xi yi ke da xue xue bao bian wei hui] 29 (3): 334–7. PMID 10684107. 
  50. ↑ Takase, H; Imanishi, K; Miura, O; Yumioka, E; Watanabe, H (1989). "Features of the anti-ulcer effects of Oren-gedoku-to (a traditional Chinese medicine) and its component herb drugs". Japanese journal of pharmacology 49 (3): 301–8. doi:10.1254/jjp.49.301. PMID 2747035. 
  51. ↑ Nam, KN; Jung, HJ; Kim, MH; Kang, C; Jung, WS; Cho, KH; Lee, EH (2009). "Chunghyuldan attenuates brain microglial inflammatory response". Canadian journal of physiology and pharmacology 87 (6): 448–54. doi:10.1139/y09-028. PMID 19526039. 
  52. ↑ Chang, GT; Min, SY; Kim, JH; Kim, SH; Kim, JK; Kim, CH (2005). "Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs". Vascular pharmacology 43 (4): 283–8. doi:10.1016/j.vph.2005.08.014. PMID 16226922. 
  53. ↑ Fuwa, T; Kosoto, H; Tani, T (2005). "Use of crude drugs in "PiWeiLun" in comparison to those used in "NeiWaiShangBianHuoLun"". Yakushigaku zasshi. the Journal of Japanese history of pharmacy 40 (1): 13–21. PMID 16217902. 
  54. ↑ Hamada, T (1993). "Studies on the medicinal plant in the "Sambutsu-cho" of Higo Province possessed by the Kumamoto Clas (I): on the medicinal trees". Yakushigaku zasshi. the Journal of Japanese history of pharmacy 28 (1): 6–11. PMID 11639720. 
  55. ↑ Hubík, J; Spilková, J (1993). "Herbal drugs in Kampo preparations". Ceskoslovenska farmacie 42 (2): 65–7. PMID 8402959. 
  56. ↑ 56.0 56.1 Li, CY; Lu, HJ; Lin, CH; Wu, TS (2006). "A rapid and simple determination of protoberberine alkaloids in cortex phellodendri by 1H NMR and its application for quality control of commercial traditional Chinese medicine prescriptions". Journal of pharmaceutical and biomedical analysis 40 (1): 173–8. doi:10.1016/j.jpba.2005.06.017. PMID 16061339. 
  57. ↑ 57.0 57.1 57.2 Su, X; Kong, L; Li, X; Chen, X; Guo, M; Zou, H (2005). "Screening and analysis of bioactive compounds with biofingerprinting chromatogram analysis of traditional Chinese medicines targeting DNA by microdialysis/HPLC". Journal of Chromatography A 1076 (1–2): 118–26. doi:10.1016/j.chroma.2005.04.031. PMID 15974077. 
  58. ↑ 58.0 58.1 58.2 58.3 58.4 58.5 58.6 58.7 58.8 58.9 Wang, M; Ji, TF; Yang, JB; Su, YL (2009). "Studies on the chemical constituents of Phellodendron chinense". Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 32 (2): 208–10. PMID 19504962. 
  59. ↑ 59.0 59.1 59.2 59.3 59.4 59.5 Min, YD; Kwon, HC; Yang, MC; Lee, KH; Choi, SU; Lee, KR (2007). "Isolation of limonoids and alkaloids from Phellodendron amurense and their multidrug resistance (MDR) reversal activity". Archives of pharmacal research 30 (1): 58–63. doi:10.1007/BF02977779. PMID 17328243. 
  60. ↑ 60.0 60.1 60.2 Miyake, M; Inaba, N; Ayano, S; Ozaki, Y; Maeda, H; Ifuku, Y; Hasegawa, S (1992). "Limonoids in Phellodendron amurense (Kihada)". Yakugaku Zasshi 112 (5): 343–7. PMID 1403667. 
  61. ↑ 61.0 61.1 Zhou, HY; Wang, D; Cui, Z (2008). "Ferulates, amurenlactone A and amurenamide A from traditional Chinese medicine cortex Phellodendri Amurensis". Journal of Asian natural products research 10 (5–6): 409–13. doi:10.1080/10286020801966534. PMID 18464078. 
  62. ↑ Kuo, PC; Hsu, MY; Damu, AG; Su, CR; Li, CY; Sun, HD; Wu, TS (2004). "Flavonoids and coumarins from Leaves of Phellodendron chinense". Planta medica 70 (2): 183–5. doi:10.1055/s-2004-815500. PMID 14994201. 
  63. ↑ 63.0 63.1 Wu, TS; Hsu, MY; Kuo, PC; Sreenivasulu, B; Damu, AG; Su, CR; Li, CY; Chang, HC (2003). "Constituents from the leaves of Phellodendron amurense var. wilsonii and their bioactivity". Journal of Natural Products 66 (9): 1207–11. doi:10.1021/np030034v. PMID 14510598. 
  64. ↑ Cui, WS; Tian, J; Ma, ZJ; Guo, YQ; Wang, JH; Li, X (2003). "A new isocoumarin from bark of Pellodendron chinense". Natural product research 17 (6): 427–9. doi:10.1080/14786410310001617695. PMID 14577693. 
  65. ↑ Lee, JH; Lee, DH; Yu, HE; Kim, JH; Lee, JS (2006). "Isolation and characterization of a novel glutathione S-transferase-activating peptide from the oriental medicinal plant Phellodendron amurense". Peptides 27 (9): 2069–74. doi:10.1016/j.peptides.2006.03.004. PMID 16624447. 

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