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Family Betulaceae
Arnus
Alnus japonica Steud.
JAPANESE ALNUS


Scientific names Common names
Alnus harinoki Siebold Arnus (If.)
Alnus japonica (Thunb.) Steud. Japanese alder (Engl.)
Alnus reginosa Nakai Japanese alnus (Engl.)
Betula japonica Thunb.  
Alnus japonica (Thunb.) Steud. is an accepted name. The Plant List

Other vernacular names
CHINESE: Ri ben qi mu.
JAPANESE: Han no ki.

Botany
Arnus is a small- to medium-sized deciduous tree growing to a height of 15 meters. Leaves are simple, alternate, narrow-elliptic, acuminate, wedge-shaped at the base, up to 12 centimeters long, glossy and dark green above and pale underneath, the margins slightly toothed. Flowers are staminate, in long catkins; the pistillate flowers are in short catkins, becoming woody cones with 5-lobed scales and 2-winged nutlets. Fruit is a small nut, compressed, one-seeded

Distribution
- Indigenous to Korea.
- Grows in Baguio and other parts of the Mountain Province.
- Propagated by seed or grafting.


Constituents
- Two diarylheptanoids, oregonin and hirsutanone were isolated by bioassay-guided fractionation of the methanol extracts of the leaves of Alnus japonica Steud and their structures were elucidated from their spectroscopic data. Compounds exhibited significant low-density lipoprotein (LDL)-antioxidant activities.
- Study of ethanol extract of stem bark isolated a new diarylheptanoid named alnuheptanoid A [(5S)-7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-5-methoxyheptan-3-one] (8), along with seven known diarylheptanoid derivatives: platyphyllenone (5), (5S)-1,7-bis(4-hydroxyphenyl)-5-methoxyheptan-3-one (6), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one (7), hirsutenone (9), (5R)-O-methylhirsutanonol (10), hirsutanonol (11) and oregonin (13), three triterpenes: α-amyrin (1), betulinaldehyde (3) and betulinic acid (4), and two sterols: β-sitosterol (2) and daucosterol (12). (20)
- Crude extract of stem bark isolated two novel diarylheptanoids, known as alnuside C (2) and alnuside D (3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-β-D-glucopyranoside (1), oregonin (4) and hirsutanone (5). (see study below) (21)

Properties
- Studies suggest antioxidant, hepatoprotective, cytotoxic, anticancer, antiatherosclerotic, antiviral, anti-trypanosomal, antiproliferative, pro-apoptotic properties.

Parts used
Stem bark, leaves.

Uses
Folkloric
- No reported folkloric medicinal use in the Philippines.
- Popular folk medicine in Korea, used for cancer, gastric disorders, hepatitis and fatty liver.
- Various species of alder, including this species, seem to contain antitumor compounds.
- In Oriental medicine, bark used for fever, hemorrhage, gastroenteric disorders, lymphatic disease and cancers. (15)
- Cortex extract traditionally used for purifying blood and treating enteritis, diarrhea, hematochezia, and cut wounds. (30)

Other uses
- Dye: Bark yields a dye.
- Fuel: Source of firewood.
- Wood - Close grained; used for turnery. Suitable for making small furniture, and charcoal for gunpowder. (26)
- Barrier or support:
Used as living posts. (26)


Studies
Hepatoprotective / Antioxidant: Alnus japonica showed antioxidant activity and hepatoprotective effects against acetaminophen-induced cytotoxicity in cultured hepatocytes in vitro. (4)
Cytotoxic / Diarylheptanoids: Study isolated 10 compounds from the bark of Alnus japonica. The diarylheptanoids showed potent cytotoxic activities against murine B16 melanoma cells and human SNU-C1 gastric cancer cell line. (1)
Anti-Influenza / Diarylheptanoids / Bark: Study isolated two rare acylated diarylheptanoids from the bark of A japonica – oregonoyl A and oregonoyl B, with nine known compounds. Platyphyllone, was strongly active, and platyphyllonol-5-xylopyranoside was moderately active on antiviral testing, compared with positive control, zanamivir. (5)
Anti-Atherosclerosis / Diarylheptanoids: Study isolated reported the inhibitory effects of two diarylheptanoids from the methanolic extracts of Alnus japonica leaves on the expression of adhesion molecules in human umbilical vein endothelial cells. Results suggest the compounds may be useful in prevention and treatment of atherosclerosis.
Antioxidant: Study isolated naturally occurring bioactive compounds from AJ that showed significant radical-scavenging antioxidant activity in a concentration-dependent manner.
Antioxidant / Anti-LDL Oxidation / Anti-Inflammatory: Study isolated 5-O-methylhirsutanonol (5-MH) from the leaves of A japonica which exhibited antioxidant activities on Cu2+ and AAPH-mediated LDL oxidation and well as macrophage-mediated LDL oxidation. 5-MH also suppressed the expression of inflammation-associated genes, such as tumor necrosis factor alpha, COX-2 and IL-1ß.
Hirsutenone / Atopic Dermatitis / Bark: Study isolated hirsutenone from the bark of Alnus japonica. Results showed hirsutenone may specifically inhibit calcium-activated processes in both T cells and mast cells and presents a potential for a new topical drug for atopic dermatitis, probably through a calcineurin inhibitor-mimicking mechanism. (9)
Anti-Influenza Component / Bark: Study of bark isolated four lupane-type triterpenes (1-4) and one steroid (5). Compound 3, betulinic aldehyde, exhibited a particularly strong anti-influenza effect against KBNP-0028 relative to a positive control. (10)
Oregonin / I/R Induced Mesentery Oxidative Stress / Inhibition of NADPH Oxidase Activation/ Bark: Study suggests that ORG restrained I/R-induced ROS production might be correlated to its inhibitive effect on NADPH activation. (11)
Diarylheptanoids / Inhibition of Papain-Like Protease of SARS: The papain-like protease, which controls replication of the acute respiratory syndrome coronavirus is identified as the potential drug target for the treatment of SARS. Of the nine diarylheptanoids isolated from Alnus japonica, hirsutenone (compound 2) showed the most potent PL inhibitory effect. (12)
Atopic Dermatitis / Leaves and Bark: Study evaluated the immunomodulatory effect of A. japonica in a model of atopic dermatitis in NC/Nga mice. Leaf and bark extract suppressed the development of AD-like skin lesions, with decrease in blood eosinophils and decrease in serum IgE and Th2-related cytokine levels. Results suggest the leaf and bark extract may prove useful in the treatment of atopic dermatitis and other allergic skin diseases. (13)
Cytotoxicity / Oregonin and Hirsutanone: Study evaluated the cytotoxic effects of four different extracts from A. japonica on Caco-2 cells using MTT assay. Oregonin and hirsutanon from the four extracts, index ingredients of Alnus japonica, were analyzed with HPLC and physiochemical studies. In cell cytotoxicity study, the water extract showed highest cytotoxicity. The 70% methanol extract showed highest content for both oregonin and hirsutanone. (15)
Anticancer / Antioxidant / Caspase-Dependent Pathway: Study evaluated A. japonica extracts for in vitro antioxidant and anticancer effects in AGS human gastric carcinoma cell lines. Results showed ethanol extracts have greater antioxidant activity than water extracts. The ethanol extract inhibited cell growth and induced cell death by increasing reactive oxygen species production in AGS cells. The extract triggered apoptosis when caspase-8, 7, 3 and PARP were activated. Results suggest a potential strategy for clinical chemotherapy. (16)
Dyeing Properties / Bark and Heartwood: Study evaluated the dyeing properties of cotton and silk fabrics dyed with A. japonica bark and heartwood extracts. Results showed tannin to be the major colorant component. Silk dye intake was better than that of cotton. Although washing fastness was not good, light, dry cleaning, and perspiration fastness were moderate. Also, rubbing fastness was moderately good grade. Dyed fabrics showed very good antimicrobial abilities of 99.9% against S. aureus and K. pneumonia. (17)
Hepatoprotective / Antioxidant / Bark: Study of Alnus japonica bark isolated one new diarylheptanoid, named alusenone (1A), and 11 known one (1B-2-11). Mixtures 1, 2-6, 10 and 11 showed good antioxidative and hepatoprotective effects compared to controls. (19)
Anti-Trypanosomal / Bark: A crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Study isolated two novel diarylheptanoids and three known compounds. Among the isolated diarylheptanoid, oregonin and hirsutanone exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC50 of 1.14 and 1.78 µM, respectively. (see constituents above) (21)
• Epihirsutanonol / Hepatoprotective Activity / Bark: Study isolated a new diarylhelptanoid, epihirsutanonol (1) from the bark of Alnus japonica, along with two known ones. The new compound showed significant hepatoprotective activity on the bass of t-butylhydroperoxide induced hepatocyte injury in vitro assay. (22)
• Cyclic Diarylheptanoids / Antioxidant / Anti-Inflammatory / Stem BarK: Study of EtOAc fraction of stem bark of Alnus japonica yielded a new cyclic diarylheptanoid, alnuheptanoid B (3), along with four known cyclic diarylheptanoids viz., myricanone (1), (+)-S-myricanol (2), myricanone 5-O-ß-D-glucopyranoside (4), and (+)-S-myricanol 5-O-ß-D-glucopyranoside (5). Compounds were assessed for anti-inflammatory and antioxidant activity using carrageenan induced rat paw edema method and DPPH assay, respectively. Results showed significant antioxidant activity compared to standard antioxidant propyl gallate at concentration of 50 µM. Compound 2 demonstrated anti-inflammatory activity at dose of 10 mg/kg compared with indomethacin control. (23)
• Pro-Apoptotic / Antiproliferative / Human Leukemia Cell Lines / Bark: Study evaluated the antiproliferative activity of hirsutanone (Hir) and oregonin ()re) in human cancer cell lines. A cytotoxicity study using a panel of 12 human cancer and 4 normal cell lines showed Hir exhibited potent antiproliferative activity against 4 leukemia (Jurkat, U937, THP-1, and HL-60) and 2 colon cancer cell lines (HCT-15 and colo205). The Hir also exhibited antiproliferative actions via caspase-dependent apoptotic cell death. (24)
• Diarylheptanoids / Curcumin Analogues / Pancreatic Cancer Cell Line: Isolated diarylheptanoids from the plants exhibited inhibition of growth of PANC-1 (KRAS heterozygous G12E, TP53 homozygous P72R and R273H) pancreatic cancer cell line. Mechanism was attributed to the inhibition of FoxM1 transcription factor signaling axis. (25)
• Ameliorative Effect on Colitis / Anti-Inflammatory / Attenuation of Intestinal Barrier Disruption / Bark: IBD (Inflammatory bowel disease) is a chronic inflammation of the GIT caused by high levels of pro-inflammatory cytokines and epithelial barrier dysfunction. Study evaluated the effect of ethanol extract of A. japonica bark on colonic mucosa injury in mice with DSS (dextran sodium sulfate)-induced colitis. Treatment ameliorated the pathological damage and histopathologic features of DSS-inudced colitis. The extract also inhibited pro-inflammatory cytokines expression. Overall results suggest the AJE inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis in vivo and human intestinal epithelial cells in vitro. Study suggests potential benefits for the treatment of IBD. (27)
- Caspase-Mediated Apoptosis / Human Gastric Carcinoma Cells: Study evaluated A. japonica extracts for in vivo antioxidant potential and anticancer effects in AGS human gastric carcinoma cell line. Antioxidant activity was evaluated by DPPH, FRAP, and ABTS assays. The ethanol extract exhibited more potent antioxidant activity than the water extract. The extract inhibited cell growth and induced cell death by increasing ROS production in AGS cells. All extracts triggered apoptosis medicated through activation of caspase-8, 7, 3, and poly-ADP ribose polymerase (PARP). Results suggest potential use as a promising strategy for treatment of gastric cancer carcinoma. (28)
• Invention / Herbal Combination as Natural Tea for Impotence: Invention relates to an invigorating herbal combination tea product for curing men's impotence. The tea is composed of a parasitic herb as first material and Alnus japonica and/or schizandrae fructus as second material. (29)
• Anticancer / Apoptosis of Human Colon Adenocarcinoma Cells / Mitochondria/Caspase Pathway: Study of an ethanol extract of Alnus japonica exhibited significant cytotoxicity in human colon adenocarcinoma HT-29 cells via induction of apoptosis through a ROS-mitochondria-caspases-dependent pathway in human HT-29 cells. (30)
• Invention: Anti-Influenza Viral Composition / Stem and Bark: Invention relates to an antiviral composition comprising bark or stem A. japonica extract and a method for preparing high activated anti-influenza viral composition. The invention suggests that the bark or stem extract has low toxicity to normal cells, while having an exscellent antiviral effect even at low concentration, with potential for preventing and treating influenza viral infection. (31)
• Hirsutenone / Anti-Prostate Cancer / Inhibition of Akt: Study showed that hirsutenone, a bioactive compound in Alnus japonica, exhibits anti-cancer effects against prostate cancer through a direct physical inhibition of Akt1/2. Hirsutenone strongly induces apoptotic cell death in both PC3 and LNCaP cells. Results suggest hirsutenone suppresses human prostate cancer by targeting Akt1 and 2 via inhibition by direct binding in an ATP-noncompetitive manner in vitro and ex vivo. (32)

Availability
- Wildcrafted.
- Cultivated.
- Seeds in the cybemarket.

Updated January 2019 / September 2016

© Godofredo Stuart / StuartXchange

Additional Sources and Suggested Readings
(1)
Cytotoxic activities of diarylheptanoids from Alnus japonica / Sun Eun Choi et al / Archives of Pharmacal Research • Volume 31, Number 10 / October, 2008 / DOI 10.1007/s12272-001-2108-z
(2)
Alnus japonica / Plants For A Future
(3)
Further investigation of the phenolic components
(4)
Hepatoprotective and antioxidant effects of Alnus japonica extracts on acetaminophen-induced hepatotoxicity in rats / Sang Tae Kim et al / PTR. Phytotherapy research, 2004; (18)12: pp. 971-975 /
PubMed ID 15742342
(5)
Anti-influenza diarylheptanoids from the bark of Alnus japonica / Nguyen Huu Tung et al / Bioorganic & Medicinal Chemistry Letters, 1 February 2010; Volume 20, Issue 3: pp1000-1003 / doi:10.1016/j.bmcl.2009.12.057
(6)
Effects of Diarylheptanoids on the Tumor Necrosis Factor-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells / Jong-Min Han et al / J. Agric. Food Chem., 2007, 55 (23), pp 9457–9464 / DOI: 10.1021/jf072157h
(7)
Diarylheptanoid and Flavonoid with Antioxidant Activity from Alnus japonica Steud on DPPH Free Radical Scavenging Assay
(8)
Effect of 5- O-Methylhirsutanonol on Nuclear Factor-κB-Dependent Production of NO and Expression of iNOS in Lipopolysaccharide-Induced RAW264.7 Cells / Jon-Min Han et al / J. Agric. Food Chem., 2008, 56 (1), pp 92–98 / DOI: 10.1021/jf0721085
(9)
Suppression of T cell activation by hirsutenone, isolated from the bark of Alnus japonica, and its therapeutic advantages for atopic dermatitis / Joo SS, Kim S G et al / Eur J Pharmacol. 2009 Jul 1;614(1-3):98-105. Epub 2009 May 3.
(10)
An Anti-Influenza Component of the Bark of Alnus japonica / Nguyen Huu Tung, Hyuk-Joon Kwon, Jae-Hong Km, Jeong Chan Ra, Jeong Ah Kim, and Young Ho Kim / Archives of Pharmacal Research, March 2010, Volume 33, Issue 3, pp 363-367
(11)
Oregonin from the bark of Alnus japonica restrained ischemia-reperfusion induced mesentery oxidative stress by inhibiting NADPH oxidase activation / Nguyen Huu Tung, Kai Sun, Jing-Yu Fan, Yukihiro Shoyama,* andJing-Yan Han* / DOI: 10.1111/micc.12147
(12)
Diarylheptanoids from Alnus japonica Inhibit Papain-Like Protease of Severe Acute Respiratory Syndrome Coronavirus / Ji-Young Park, Hyung Jae Jeong, Jang Hoon Kim, Young Min Kim, Su-Jin Park, Doman Kim, Ki Hun Park, Woo Song Lee,* and Young Bae Ryu* / Biol. Pharm. Bull. 35(11) 2036–2042 (2012) Vol. 35, No. 11
(13)
Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice. / Sun Eun Choi, Kwan Hee Park, Mi Sook Jeong, Han Hyuk Kim, Do Ik Lee, Seong Soo Joo, Chung Soo Lee, Hyoweon Bang, Young Wook Choi, Mi-Kyung Lee, Seong Jun Seo, Min Won Lee / Journal of Ethnopharmacology, 2010 / DOI: 10.1016/j.jep.2010.12.024
(14)
Alnus japonica (Thunb.) Steud. / Synonyms / The Plant List
(15)
Quantitative Analysis and Preformulation of Extracts from Alnus Japonica
/ Jong-Suep Baek, Hee-Chul Kang, Chang-Gu Keum, Ji-Ho Lim, Chan-Ju Hwang, Young-Guk Na, N.H. Tung, Young-Ho Kim and Cheong-Weon Cho / Journal of Pharmaceutical Investigation, 2011; Vol 41, No 4: pp 227-232
(16)
Anticancer effect of Alnus japonica extracts through the caspase-dependent pathway / BI You, SE Kim, YS Kim, JW Hwang, NJ Jeon, X Dong / PJ Park 1Planta Med 2015; 81 - PM_81 / DOI: 10.1055/s-0035-1565458
(17)
Dyeing Properties and Functionalities of Alnus japonica Bark and Heartwood Extracts / Sa, A-Na; Choi, Hyo Jin; Lee, Jung Soon / Textile Science and Engineering, Vol 50, Issue 5 (2013) pp 283-291 / DOI : 10.12772/TSE.2013.50.283
(18)
Bioactive constituents and medicinal importance of genus Alnus / Sushil Chandra Sati, Nitin Sati, and O. P. Sati / Pharmacogn Rev. 2011 Jul-Dec; 5(10): 174–183. / doi: 10.4103/0973-7847.91115
(19)
Antioxidative and Hepatoprotective Diarylheptanoids from the Bark of Alnus japonica
/ Nguyen Huu Tung, Sang Kyum Kim, Jeong C Ra, Young Ho Kim / Planta Medica 76(6):626-9 · November 2009 / DOI: 10.1055/s-0029-1240595
(20)
Alnuheptanoid A: a new diarylheptanoid derivative from Alnus japonica / Sabrin R.M. Ibrahim, Mostafa A. Fouad, Ahmed Abdel-Lateff, Tatsufumi Okino & Gamal A. Mohamed / Natural Product Research, Volume 28, 2014 - Issue 20
(21)
Anti-Trypanosomal Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica / Nguyen Huu Tung et al / Am. J. Chin. Med., 2014; 42(5): 1245 / DOI: http://dx.doi.org/10.1142/S0192415X14500785
(22)
A new diaarylheptanoid from the bark of Alnus japonica / Nguyen Huu Tung, Jeong d Ra, Dong Hwan Sohn, Young Ho Kim / Journal of Natural Products Research, Oct 2010; 12(10): pp 921-924 / DOI: 0.1080/10286020.2010.507196
(23)
Antioxidant and Anti-Inflammatory Cyclic Diarylheptanoids from Alnus japonica Stem Bark / Sabrin R.M. Ibrahim, Gamal A. Mohamed, Amgad I. M. Khedr and Bader M. Aljaeid / Iranian Journal of Pharmaceutical Research, 2017;16 (Special Issue): pp 83-91
(24)
Pro-Apoptotic Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica in Human Leukemia Cell Lines / Takuhiro Uto, Nguyen Huu Tung, Regina Appiah-Opong, Abigail Aning, Osamu Morinaga, Dominic Edoh, Alexander K Nyarko and Yukihiro Shoyama / The American Journal of Chine Medicine, 2015; Vol 43, No 4; pp 757-767 / https://doi.org/10.1142/S0192415X15500470
(25)
Curcumin analogues extracted from Alpinia officinarum and Alnus japonica inhibited the FoxM1 signalling axis in a pancreatic cancer cell line / David Orchard Webb . Biotechnology, Healthcare, Science / Aug 2017
(26)
Alnus japonica / WorldAgroForestry
(27)
Ameliorative Effect of Alnus japonica ethanol extract on colitis through the inhibition of inflammatory responses and attenuation of intestinal barrier disruption in vivo and in vitro / Jin Hua Chi, Young Ho Kim, Dong Hwan Sohn,, Geom Seog Seo, Sung Hee Lee / Biomedicine & Pharmacotherapy Dec 2018; 108: pp 1767-1774 / https://doi.org/10.1016/j.biopha.2018.10.050
(28)
Induction of caspase-mediated apoptosis using Alnus japonica extracts in AGS human gastric carcinoma cells / Seong-Eun Kim, Yon-Suk Kim, Woen-Bin Shin, Jin-Su Park, Sang-Ho Moon, Byong-Tae Jeon, Pyo-Jam Park / J Appl Biomed., 2018; 16: pp 198-207
(29)
Invention: A natural tea for curing men's impotence and a method for manufacturing the same  / EP Application / EP1150574A1
(30)
Extract of Alnus japonica Induces Apoptosis of Human Colon Adenocarcinoma Cells through the Mitochondria/Caspase Pathway / Jeon Byoung-Kook, Baik Soon-Ki, Woo Won-Hong, Mun Yeun-Ja / Journal of Physiology & Pathology in Korean Medicine, April 2012; 26(2): pp 199-205
(31)
Anti-influenza viral composition containing bark or stem extract of Alnus japonica  / US Grant / US8470378B2
(32)
Hirsutenone in Alnus extract inhibits akt activity and suppresses prostate cancer cell proliferation / Soouk Kang, Jong Eun Kim, Yan Li, Sung Keun Jung, Nu Ry Song, N. R. Thimmegowda, Bo Yeon Kim, Hyong Joo Lee, Ann M. Bode, Zigang Dong, Ki Won Lee / Molecular Carcinogenesis, 2015; 54(11): pp 1354-1362 /  https://doi.org/10.1002/mc.22211

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