Haninjin

Last Updated: September 28 2022

Artemisia iwayomogi (Haninjin) has limited traditional use, but as of late is being investigated for anti-cancer properties. At least one study suggests possible fat-burning effects, and immune-system interactions may be present.

Haninjin is most often used for




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    1.

    Sources and Composition

    1.1

    Composition

    • Iwayomin[4]
    • Scopolin (0.403% dry weight) and its aglycone Scopoletin (1.509%)[4][5][6]
    • Genkwanin[6] and Jaceoside[6]
    • Quebrachitol[6]
    • 2,4-dihydroxy-6-methoxyacetophenone[6] (and its 4-O-b-D-glucoside)[4]
    • Fraxidin 8-O-bD-glucoside[4]
    • Myrciaphenone A[4] and Erythroxyloside B[4]
    • Vulgarone B[7]
    • Coniferin[4]
    • Citrusin C[4]
    • Tachioside[4]
    • 3-O-Methylisosecotanapartholide and Isosecotanapartholide[5]
    • Caffeic Acid (methyl ester; 0.122%)[5]
    • Benzoic Acid[4]
    • Chlorogenic Acid[6]
    • Dibromo-4-methoxybiphenyl[8]
    • Glycocholic Acid[8]
    • Bomame[8]
    • Enopyranoside derivative (concentrated in ethanolic extract)[8]
    • Camphor (concentrated in ethanolic extract)[8] and other aromatic essential oils such as Borneol, 1,8-Cineole, β-Caryophyllene, and Campehene[9]

    Various bioactives, but it is not really known which are seen as the 'main' bioactive components of Artemisia Iwayomogi

    Some bioactive polysaccharides:

    • AIP1, a polysaccharide under 2kDa in size[10][11]

    image

    2.

    Cardiovascular Health

    2.1

    Lipids

    Administration of 200mg/kg of a 95% ethanolic extract to mice for 8 weeks concurrent with a high fat diet does not appear to influence circulating triglyceride nor cholesterol levels despite plasma non-esterified fatty acids (NEFA) being reduced from a 71% increase (high fat control) to 19% (Artemisia).[8]

    3.

    Interactions with Glucose Metabolism

    3.1

    Interventions

    A study giving 200mg/kg of a 95% ethanolic extract to mice that confirmed weight loss during a high fat diet failed to find improvements in circulating glucose levels.[8]

    4.

    Interactions with Skeletal Muscle

    4.1

    Mechanisms

    A 95% ethanolic extract of Artemisia Iwayomogi appears to active PPARδ (delta) with an EC50 value of 7mcg/mL in a dose-dependent manner, although a 50% ethanolic extract and water extract failed to show effects; it appeared to have maximal stimulation approaching the active drug GW501516, although required a higher concentration to do so. This extract bound to the ligand-binding domain directly.[8] These effects were observed in incubated skeletal muscles (with upregulation of the downstream targets of CPT1, PDK4, PGC1α, and UCP3) all of which were abolished by blocking the PPARδ receptor, and these were though to underlie how 200mg/kg oral intake of this ethanolic extract to mice fed a high fat diet for 8 weeks where the rate of weight gain was significantly attenuated and the aforementioned downstream targets were confirmed to be upregulated in skeletal muscle biopsy.[8] Although no lone molecule appeared causative for these effects, the molecule known as Dibromo-4-methoxybiphenyl appeared in the ethanolic extract (3.55%) and shares weak structural similarity to GW501516.

    This 95% ethanolic extract may also enhance glucose uptake into the skeletal muscle cell, although by insulin-dependent means and independent of the PPARδ receptor.[8]

    5.

    Inflammation and Immunology

    5.1

    Mechanisms

    In tests on activated macrophages, the methanolic extract of the bark of Artemisia Iwayomogi inhibits LPS-stimulated NO release in a concentration dependent manner with 20, 40, and 80mcg/mL inhibiting 23.1%, 74.3%, and 94.2% of nitric oxide; the inhibitory compounds were further concentrated in either an EtOAc extraction or ethyl ether, where 50mcg/L of both of these abolished nitric oxide release (over 100% inhibition)[12] and a later study isolated the active compounds as 3-O-methyl-isosecotanapartholide (IC50 3.64mcg/mL) and isosecotanapartholide (2.81mcg/mL);[13] two compounds similarly named but structurally different than Parthenolide from Feverfew.

    In a human gingival fibroblast cells (acquired by biopsy), Artemisia Iwayomogi appears to downregulate 19% of the gene products upregulated by proinflammatory LPS while upregulating 48% of the genes that are downregulated by LPS.[5] The pathways that seemed to be implicated most include the Focal Adhesion pathway, the Cytokine-Cytokine receptor interation pathway, and MAPK signalling.[5] At 20-80mcg/mL Artemisia Iwayomogi (70% ethanolic extract) noted suppression of IL-6 release induce by TNF-α at 40mcg/mL or above, with some efficacy coming from isolated Scopolin and Scopoletin (0.1-1uM).[5]

    Bioactives may have anti-inflammatory effects, with the suppression of active macrophages being fairly potent in vitro

    5.2

    Immune Cells

    In mouse thymocytes and splenocytes, a low concentration of 2g/mL AIP1 (polysaccharide) appears to attenuate the rate of which thymocytes die in culture over a period of 12 days; there was no increase in thymocyte count, suggesting anti-apoptoic yet not mitogenic effects.[10][14] These effects were associated with less DNA fragmentation, and preliminarly thought to be mediated via downregulation of the Fas receptor (and less activity of the Fas/FasL death pathway),[10] and downregulation of Fas mRNA has been noted elsewhere in thymocytes despite being induced by the TCDD toxin (known to induce apoptosis of thymocytes with an upregulation of Fas playing a pivotal role).[15]

    The polysaccharide in Artemisia Iwayogoi (may also be in other Artemisia species) appears to not have mitogenic (immune cell proliferating) effects but instead attenuates the rate of which cells undergo apoptosis (lyse)

    This same polysaccharide fragment appears to have suppressive effects an the antigen-presenting dendritic cells in a concentration dependent manner, with 1mcg/mL reducing the percentage of CD11c+ positive immature Dendritic cells from 12.56% (vehicle cultures) to 9.04% (AIP1 culture) and reducing the T-cell stimulating potential of these cells.[11] This study also noted downregulation of TRAF5-like protein mRNA (2.14 fold), PKM2 mRNA (2.22 fold), and Coactosin-like protein 1 (2.61 fold) with no influence on HGPRT.[11] A reduction in these dendritic cells has been noted in vivo following injections of 0.5–50mg/kg in a pulsatile manner.[16]

    May have some actions against antigen-presenting cells

    When a water extract in injected into mice at a dose of 1-1000mg/kg bodyweight prior to injection of 8mg/kg of Compound 48/80 (mast cell degranulator, able to induce a fatal allergic reaction) was able to reduce lethality in a dose-dependent manner with 500-1000mg/kg abolishing lethality and 1g/kg injected shortly after Compound 48/80 having similar effects.[17] In vitro, this extract was able to dose-dependently reduce histamine release from both IgE and Compound 48/80 in a dose-dependent manner and 100mcg/mL of the extract incubated with rat plasma Mast Cells (RPMCs) abolished the increase in intracellular calcium and greatly attenuated TNF-a and IL-6 release from human mast cells possibly secondary to inhibiting the effects of p38 MAPK and NF-kB.[17] These results have been replicated both in vivo and in vitro, where the increase in TNF-α and IL-6 secretion from mast cells were reduced by 67% and 57% at a concentration of 1mg/mL.[18]

    At least one study has noted that injections of a low-weight polysaccharide (AIP1) can dose-dependently reduce eosinophile infiltration into lung tissue following injection of an antigen (Ovalbumin) and reduce serum levels of IgE and TNF-α in lung tissue.[16]

    Possibly potent anti-allergic effects

    6.

    Interactions with Oxidation

    6.1

    General

    Artemisia Iwayomogi appears to have peroxynitrate (ONOO-) radical scavenging properties, which according to this one study was the most potent of a scan of 138 herbs (listed in full text) with 93.12% inhibition at 10mcg/L in vitro;[6] Artemisia slightly outperformed Codonopsis Pilosula (90.33%), Geum japonicum (91.05%), and Ligularia fischeri (88.68%), and Artemisia had an IC50 for scavenging peroxynitrate of 1.79+/-041ug/mL which was mostly due to chlorogenic acid (IC50 0.52+/-0.04uM), genkwanin (1.01+/-0.10uM), and scopoletin (1.03+/-0.15uM).[6]

    Potentially very potent in inhibiting peroxynitrate formation, outperforming other antioxidant herbs

    7.

    Interactions with Organ Systems

    7.1

    Liver

    One of the few traditional uses of the herb Artemisia Iwayomogi is in the treatment of liver diseases.[10]

    Fas gene expression appears to positively mediate fibrogenesis in the liver[19] with diet-induced hepatic steatosis (fatty liver) sensitizing this receptor;[20] siRNA interference with this receptor has been shown to exert a protective effect against fibrosis and fulminant hepatitis.[21] One study in Thymocytes noted downregulation of Fas after incubation with the AIP1 polysaccharide,[10] and was hypothesized to play a role in the liver.

    Another theorized mechanism (not yet demonstrated) is downregulation or inhibition of FXR and SREBP-1c, which was thought as the benefits of Artemisia mimicked that of UDCA used as active control on one study of bilt duct litigation[22] which is the mechanism UDCA benefits this model.[23]

    Fas receptor inhibition may play a role in preventing fibrosis, but despite its confirmed role in pathology it has not been found to be a major locus for the benefits of Artemisia Iwanoyogi; SREBP-1c may also be implicated

    In rats given a bile duct litigation (inducing Fibrosis via cholestatic liver injury) the water extract of Artemisia Iwayomogi at 25-50mg/kg for 14 days was able to ameliorate the increase in white blood cells (no influence on platelets or RBCs), triglycerides, bilirubin, and lipid peroxidation biomarkers in serum (MDA) all slightly outperforming the active control of 25mg/kg UDCA.[22] In other studies on fibrosis (although using CCL4 toxicity as a means to induce fibrosis) 50mg/kg of the water extract given orally in a rehabilitative manner appears to nearly normalized fibrotic scores.[24][25]

    Upon histological examination staining for PDGF-β, TGF-β, and α-SMA proteins and mRNA appeared to be significantly reduced to the same degree as UDCA and the scores for portal inflammation and fibrosis (modified Knodell score outlined here[26]) were reduced in a dose-dependent manner.[22] These histopathological changes are similar to previous studies in CCL4 induced fibrosis.[25][24]

    A relatively low oral dose of the water extracts appears to be highly anti-fibrotic in research animals

    Two studies have been conducted comparing the protective effects of Artemisia Iwayomogi (Haninjin) and Artemisia capillaris (Injinho), both seen as protective of the liver, with Iwayonogi appearing to be more potent in protecting the liver form fibrosis induce by CCL4 toxin[24] and in alcohol-induced liver injury.[27]

    8.

    Interactions with Cancer

    8.1

    Oral

    One study using the KB oral epidermoid carcinoma cell line, that the essential oils of Artemisia Iwayomogi were able to induce apoptosis via the mitochondrial capsase pathway and that this was mostly due to activation of MAPK.[28]

    References
    3.^Lee MY, Doh EJ, Park CH, Kim YH, Kim ES, Ko BS, Oh SEDevelopment of SCAR marker for discrimination of Artemisia princeps and A. argyi from other Artemisia herbsBiol Pharm Bull.(2006 Apr)
    4.^Ding Y, Liang C, Yang SY, Ra JC, Choi EM, Kim JA, Kim YHPhenolic compounds from Artemisia iwayomogi and their effects on osteoblastic MC3T3-E1 cellsBiol Pharm Bull.(2010)
    6.^Kim AR, Zou YN, Park TH, Shim KH, Kim MS, Kim ND, Kim JD, Bae SJ, Choi JS, Chung HYActive components from Artemisia iwayomogi displaying ONOO(-) scavenging activityPhytother Res.(2004 Jan)
    7.^Chung EY, Byun YH, Shin EJ, Chung HS, Lee YH, Shin SAntibacterial effects of vulgarone B from Artemisia iwayomogi alone and in combination with oxacillinArch Pharm Res.(2009 Dec)
    9.^Yu HH, Kim YH, Kil BS, Kim KJ, Jeong SI, You YOChemical composition and antibacterial activity of essential oil of Artemisia iwayomogiPlanta Med.(2003 Dec)
    10.^Hwang JS, Ji HJ, Koo KA, Lee NH, Yeo HK, Cheong SW, Park JH, Oh GS, Yoon CS, Youn HJAIP1, a water-soluble fraction from Artemisia iwayomogi, suppresses thymocyte apoptosis in vitro and down-regulates the expression of Fas geneBiol Pharm Bull.(2005 May)
    11.^Lee JA, Sung HN, Jeon CH, Gill BC, Oh GS, Youn HJ, Park JHAIP1, a carbohydrate fraction from Artemisia iwayomogi, modulates the functional differentiation of bone marrow-derived dendritic cellsInt Immunopharmacol.(2008 Apr)
    13.^Ahn H, Kim JY, Lee HJ, Kim YK, Ryu JHInhibitors of inducible nitric oxide synthase expression from Artemisia iwayomogiArch Pharm Res.(2003 Apr)
    14.^Hwang JS, Chung HK, Bae EK, Lee AY, Ji HJ, Park DW, Jung HJ, Cho CW, Choi HJ, Lee DS, Lee KR, Youn HJThe polysaccharide fraction AIP1 from Artemisia iwayomogi suppresses apoptotic death of the mouse spleen cells in cultureArch Pharm Res.(2003 Apr)
    17.^Kim SH, Choi CH, Kim SY, Eun JS, Shin TYAnti-allergic effects of Artemisia iwayomogi on mast cell-mediated allergy modelExp Biol Med (Maywood).(2005 Jan)
    19.^Canbay A, Higuchi H, Bronk SF, Taniai M, Sebo TJ, Gores GJFas enhances fibrogenesis in the bile duct ligated mouse: a link between apoptosis and fibrosisGastroenterology.(2002 Oct)
    20.^Feldstein AE, Canbay A, Guicciardi ME, Higuchi H, Bronk SF, Gores GJDiet associated hepatic steatosis sensitizes to Fas mediated liver injury in miceJ Hepatol.(2003 Dec)
    21.^Song E, Lee SK, Wang J, Ince N, Ouyang N, Min J, Chen J, Shankar P, Lieberman JRNA interference targeting Fas protects mice from fulminant hepatitisNat Med.(2003 Mar)
    22.^Han JM, Kim HG, Choi MK, Lee JS, Park HJ, Wang JH, Lee JS, Son SW, Hwang SY, Son CGAqueous extract of Artemisia iwayomogi Kitamura attenuates cholestatic liver fibrosis in a rat model of bile duct ligationFood Chem Toxicol.(2012 Oct)
    23.^Stedman C, Liddle C, Coulter S, Sonoda J, Alvarez JG, Evans RM, Downes MBenefit of farnesoid X receptor inhibition in obstructive cholestasisProc Natl Acad Sci U S A.(2006 Jul 25)
    25.^Park EJ, Nan JX, Kim JY, Kang HC, Choi JH, Lee SJ, Lee BH, Kim SJ, Lee JH, Kim YC, Sohn DHThe ethanol-soluble part of a hot-water extract from Artemisia iwayomogi inhibits liver fibrosis induced by carbon tetrachloride in ratsJ Pharm Pharmacol.(2000 Jul)
    26.^Sant'Anna LB, Cargnoni A, Ressel L, Vanosi G, Parolini OAmniotic membrane application reduces liver fibrosis in a bile duct ligation rat modelCell Transplant.(2011)