Angelica gigas

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Health Goals: immunity inflammation stress

Research Overview

Research on Angelica gigas spans several biomedical areas, with the most studied themes in the provided abstracts being (1) anti-cancer activity of specific constituents (notably nodakenin) and multi-herb formulations containing A. gigas (e.g., SH003), (2) anti-inflammatory and barrier-protective effects in inflammatory bowel disease (IBD) models driven by constituents such as decursin and decursinol angelate, and (3) immunomodulatory effects (macrophage, splenocyte, and NK-cell activation) again prominently featuring SH003 and nodakenin. A smaller but notable line of work links A. gigas to metabolic health indirectly via a probiotic strain (Lactiplantibacillus plantarum SKO-001) isolated from A. gigas, tested for anti-obesity effects in high-fat diet mice. In addition, a systematic review/network analysis of traditional East Asian medicine prescriptions identifies A. gigas as one of the most frequently used herbs in randomized trials of herbal medicine for female infertility, though this evidence pertains to multi-herb interventions rather than isolated A. gigas preparations.

The strongest evidence in these abstracts supports biological activity in preclinical systems: multiple mouse and cell studies report anti-inflammatory effects in DSS-induced colitis/IBD with improved disease indices, reduced pro-inflammatory cytokines, and restoration of tight junction proteins, alongside mechanistic links to innate immune signaling (e.g., inhibition of cGAS–STING activation by decursin and suppression of ROS/TXNIP/NLRP3 inflammasome signaling by decursinol angelate). For oncology, nodakenin shows in vitro cytotoxicity and in vivo tumor volume reduction in breast cancer models with mechanistic evidence implicating ER stress/PERK–CHOP signaling, Ca2+ dysregulation, ROS generation (including Nox4 involvement), and potential radiosensitization via effects on epithelial–mesenchymal transition markers. Immunologically, SH003/nodakenin demonstrate consistent stimulation of cytokine production and NF-κB activation in macrophages, enhanced splenocyte proliferation and NK activity, and mitigation of cyclophosphamide-induced immunosuppression in mice. Human-level evidence is comparatively indirect here: the infertility meta-analysis suggests herbal medicine increases pregnancy rates versus placebo, but it does not isolate the contribution of A. gigas specifically and reports generally poor CONSORT reporting quality despite overall low risk-of-bias ratings.

Key gaps include the need for well-controlled human clinical trials of standardized A. gigas extracts or purified constituents (e.g., decursin, nodakenin, decursinol angelate) to establish efficacy, dose–response, and safety in target indications suggested by preclinical work (IBD, cancer adjunctive therapy, immunosuppression-related conditions). Additional priorities are rigorous pharmacokinetic/pharmacodynamic characterization, confirmation of proposed molecular targets in vivo (e.g., direct NLRP3 binding; pathway specificity for cGAS–STING and PERK–CHOP), and evaluation of potential interactions with conventional therapies (e.g., chemotherapy, radiotherapy, immunosuppressants). For metabolic outcomes, translation is particularly preliminary because the anti-obesity study centers on a probiotic isolated from A. gigas rather than the plant itself; future work should clarify whether A. gigas components reproducibly shape microbiome function and metabolic endpoints in humans. Finally, multi-herb formulations (e.g., SH003) warrant component-resolved studies to attribute effects to specific constituents and to improve reproducibility and regulatory interpretability.

1. What conditions has Angelica gigas been studied for?

  • Obesity and metabolic abnormalities (via a probiotic strain isolated from Angelica gigas, Lactiplantibacillus plantarum SKO-001) in high-fat diet mice.

  • Breast cancer (nodakenin) in breast cancer cell lines and mouse tumor models; also studied for radioresistant breast cancer in combination with radiation.

  • Immune suppression / immune enhancement (SH003 mixture containing Angelica gigas, and nodakenin) in macrophages/splenocytes and a cyclophosphamide-induced immunosuppressed mouse model.

  • Inflammatory bowel disease / ulcerative colitis models (decursin; decursinol angelate) in DSS-induced colitis models and inflammatory signaling models (e.g., LPS/DSS paradigms).

  • Neurocognitive disorders / memory impairment (INM-176 standardized ethanolic extract) in scopolamine-induced and amyloid-β(1-42)-induced memory impairment mouse models.

  • Neuroprotection after transient ischemia (decursin and root extract) in a gerbil forebrain transient ischemia model.

  • Female infertility (as a commonly used herb in traditional East Asian medicine prescriptions; evidence summarized via RCT meta-analysis of multi-herb formulas, not Angelica gigas alone).

  • Chemotherapy-induced peripheral neuropathy (paclitaxel-induced neuropathic pain) studied with SH003 and sub-components in mice (abstract provided is truncated, so details/outcomes are incomplete).

  • Broad anti-inflammatory and chronic disease targets (review-level evidence for decursin/decursinol angelate across cancers and inflammatory conditions such as rheumatoid arthritis, diabetic retinopathy, hepatic fibrosis, allergy, Alzheimer’s disease, etc.).

2. Does it work in treating those conditions? Summarize the evidence.

  • Obesity/metabolic outcomes (animal evidence): In high-fat diet C57BL/6J mice, oral SKO-001 (a probiotic isolated from Angelica gigas) reduced obesity-related outcomes and improved metabolic abnormalities in adipose and liver tissue, “possibly via regulation of lipid metabolism.” This is preclinical evidence and does not establish efficacy in humans.

  • Breast cancer (cell + animal evidence): Nodakenin inhibited breast cancer cell viability and reduced tumor volume in mice. Mechanistically, it induced caspase-3-dependent apoptosis and engaged ER-stress signaling (PERK/CHOP), with ROS generation linked to Nox4; it also showed activity in radioresistant cells and, when combined with radiation, reduced epithelial–mesenchymal transition (EMT) phenotypes associated with radioresistance. This supports anti-tumor potential, but remains preclinical (no human trials in the abstracts).

  • Immune enhancement in immunosuppression (cell + animal evidence): SH003 (which includes Angelica gigas) and nodakenin increased cytokines (e.g., IL-12, IL-2, IL-6, TNF-α, IFN-γ), nitric oxide, iNOS expression, NF-κB p65 activation, splenic lymphocyte proliferation, and NK cell activity. In cyclophosphamide-treated mice, SH003/nodakenin increased cytokine levels in serum/spleen and alleviated immunosuppression. This suggests immunostimulatory activity in models, not proven clinical benefit.

  • IBD/colitis (animal + mechanistic evidence): In DSS-induced colitis mice, decursin (10 or 20 mg/kg daily) improved disease activity indicators (e.g., less severe pathology, reduced pro-inflammatory cytokines) and restored tight junction proteins (ZO-1, occludin, claudin-1), while inhibiting cGAS–STING pathway activation. Separately, decursinol angelate was reported to suppress NLRP3 inflammasome activation (via ROS/TXNIP/NLRP3 pathway) and improve intestinal barrier function in experimental models. These are promising preclinical findings; human efficacy is not established in the abstracts.

  • Memory impairment/Alzheimer’s-related models (animal evidence): INM-176 improved performance in passive avoidance and Morris water maze tasks in scopolamine- and amyloid-β(1-42)-induced impairment models. It inhibited acetylcholinesterase activity (hippocampal tissue in vitro/ex vivo) and reduced amyloid-β-induced astrogliosis and cholinergic neuronal loss in key brain regions. This supports cognitive/memory benefits in animal models, not yet confirmed in humans.

  • Ischemic brain injury (animal evidence): Post-treatment with decursin and root extract “saved pyramidal neurons” in the hippocampus after transient ischemia in gerbils, suggesting neuroprotection in an acute injury model.

  • Female infertility (human RCT meta-analysis, but not single-herb proof): A systematic review/meta-analysis of 18 RCTs (2,662 participants) found herbal medicine increased pregnancy rates versus placebo. Angelica gigas was the second most commonly used herb in these prescriptions, but the evidence does not isolate the effect of Angelica gigas alone. The review also noted poor reporting quality (CONSORT extension) despite generally low risk of bias.

  • Paclitaxel-induced neuropathy (insufficient details in provided abstract): The abstract indicates the question was studied in mice, but the results section is cut off, so efficacy cannot be concluded from the provided text.

3. What health benefits does it have?

  • Anti-inflammatory and barrier-protective effects (preclinical): Decursin reduced inflammatory cytokines and improved intestinal tight junction proteins in DSS colitis, while inhibiting cGAS–STING signaling; decursinol angelate was linked to suppression of ROS/TXNIP/NLRP3 inflammasome signaling and improved barrier function in experimental IBD models.

  • Potential anti-cancer activity (preclinical): Nodakenin reduced breast cancer cell viability and tumor volume in mice and promoted apoptosis via caspase-3 and ER-stress pathways; it also showed potential to help overcome radioresistance when combined with radiation (reduced EMT markers/phenotypes).

  • Immune-supporting/immunostimulatory activity (preclinical): SH003 and nodakenin activated macrophage and splenocyte responses (NF-κB p65 activation, cytokine production), increased NK cell activity, and improved immune parameters in cyclophosphamide-immunosuppressed mice.

  • Cognitive and neuroprotective effects (preclinical): INM-176 improved memory in scopolamine and amyloid-β models and inhibited acetylcholinesterase activity; decursin/root extract showed neuronal protection after transient ischemia in gerbils. Reviews cited in the abstracts also summarize broader neuroprotective/cognitive enhancement findings for root extracts and pyranocoumarins (decursin/decursinol).

  • Metabolic benefits via an associated probiotic (preclinical): SKO-001 (isolated from Angelica gigas) improved obesity-related outcomes and metabolic abnormalities in high-fat diet mice, suggesting a potential functional-food angle (strain-specific, not necessarily attributable to the herb’s phytochemicals).

  • Possible contribution to fertility-supporting formulas (indirect human evidence): In RCTs of multi-herb prescriptions, herbal medicine improved pregnancy rates versus placebo; Angelica gigas was commonly included, but its independent contribution is unknown.

4. Does it have any downsides or side effects?

  • Human safety data in these abstracts is limited. Most evidence provided is from cell and animal studies, which do not reliably predict side-effect rates in humans.

  • Infertility RCT meta-analysis (multi-herb formulas): Adverse events were reported as “generally mild and infrequent,” but this applies to herbal medicine interventions overall, not specifically to Angelica gigas as a single ingredient.

  • Potential theoretical concern—immune stimulation: SH003/nodakenin increased multiple cytokines (e.g., IL-2, IL-6, TNF-α, IFN-γ) and activated NF-κB signaling in models. While this may be beneficial in immunosuppression, it could theoretically be undesirable in conditions where immune activation is harmful (e.g., certain autoimmune/inflammatory states). This is a mechanistic caution rather than a documented clinical harm in the provided abstracts.

  • Potential drug-interaction considerations are not addressed in the abstracts. Given the bioactivity described (e.g., apoptosis pathways, inflammatory signaling, acetylcholinesterase inhibition), interactions are plausible but cannot be concluded from the provided text.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

No pharmacogenomic findings are reported in the provided abstracts. None of the studies described outcomes stratified by human genotype, nor did they identify specific genetic variants predicting benefit or harm.

  • Mechanistic notes (not pharmacogenomic evidence): Some effects depend on specific molecular targets (e.g., nodakenin effects linked to PERK/CHOP signaling and Nox4-mediated ROS; decursinol angelate proposed to bind NLRP3; decursin inhibited cGAS–STING activation). These are pathway-level findings in models and do not establish genotype-based recommendations.

References

  1. Anti-obesity effects of Lactiplantibacillus plantarum SKO-001 in high-fat diet-induced obese mice.
    Mi Jin Choi, Hana Yu, Jea Il Kim, Hee Seo, Ju Gyeong Kim, Seul-Ki Kim, Hak Sung Lee, Hyae Gyeong Cheon (2023) - European journal of nutrition
  2. Nodakenin Induces ROS-Dependent Apoptotic Cell Death and ER Stress in Radioresistant Breast Cancer
    Tae Woo Kim (2023)
  3. Herbal therapeutics for female infertility: A systematic review and meta-analysis.
    Ji-Yoon Hyun, Hyeon-Suk Jung, Ji-Yeun Park (2024) - Journal of ethnopharmacology
  4. The immune-enhancing effects of a mixture of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) or its active constituent nodakenin.
    Na-Ra Han, Kyeoung-Cheol Kim, Ju-Sung Kim, Seong-Gyu Ko, Hi-Joon Park, Phil-Dong Moon (2022) - Journal of ethnopharmacology
  5. Decursin protects against DSS-induced experimental colitis in mice by inhibiting the cGAS-STING signaling pathway.
    Jiamin Wang, Yudi Wang, Caisheng Huang, Yonghu Chen, Xuezheng Li, Zhe Jiang (2025) - Naunyn-Schmiedeberg's archives of pharmacology
  6. Decursinol angelate relieves inflammatory bowel disease by inhibiting the ROS/TXNIP/NLRP3 pathway and pyroptosis.
    Yudi Wang, Jiamin Wang, Yonghu Chen, Xuezheng Li, Zhe Jiang (2024) - Frontiers in pharmacology
  7. Analgesic Effect of SH003 and
    Ji Hwan Lee, Bonglee Kim, Seong-Gyu Ko, Woojin Kim (2022) - Current issues in molecular biology
  8. Decursin and decursinol angelate: molecular mechanism and therapeutic potential in inflammatory diseases.
    Adeeb Shehzad, Sajida Parveen, Munibah Qureshi, Fazli Subhan, Young Sup Lee (2018) - Inflammation research : official journal of the European Histamine Research Society ... [et al.]
  9. The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Aβ(1-42)-induced cognitive dysfunction in mice.
    Se Jin Park, Jun Man Jung, Hyung Eun Lee, Young Woo Lee, Dong Hyun Kim, Jong Min Kim, Jin Gyu Hong, Chang Hwan Lee, In Ho Jung, Yong-Baik Cho, Dae Sik Jang, Jong Hoon Ryu (2012) - Journal of ethnopharmacology
  10. Neuroprotective and Cognitive Enhancement Potentials of Angelica gigas Nakai Root: A Review
    Kandhasamy Sowndhararajan, Songmun Kim (2017)
  11. Therapeutic Effects of Decursin andAngelica gigasNakai Root Extract in Gerbil Brain after Transient Ischemia via Protecting BBB Leakage and Astrocyte Endfeet Damage
    Tae-Kyeong Lee, Ii-Jun Kang, Hyejin Sim, Jae-Chul Lee, Ji-Hyeon Ahn (2021)
  12. Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression.
    Joon Hyeong Cho, Jung Eun Kwon, Youngmi Cho, Inhye Kim, Se Chan Kang (2015) - Nutrients
  13. Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis.
    Tae Woo Oh, Ki-Ho Park, Hyo Won Jung, Yong-Ki Park (2015) - BMC complementary and alternative medicine
  14. Protective Effect of Decursin Extracted from Angelica gigas in Male Infertility via Nrf2/HO-1 Signaling Pathway.
    Woong Jin Bae, U Syn Ha, Jin Bong Choi, Kang Sup Kim, Su Jin Kim, Hyuk Jin Cho, Sung Hoo Hong, Ji Youl Lee, Zhiping Wang, Sung Yeoun Hwang, Sae Woong Kim (2016) - Oxidative medicine and cellular longevity
  15. Angelica gigas Nakai and Soluplus-Based Solid Formulations Prepared by Hot-Melting Extrusion: Oral Absorption Enhancing and Memory Ameliorating Effects.
    Jingpei Piao, Jae-Young Lee, Jin Bae Weon, Choong Je Ma, Hyun-Jeong Ko, Dae-Duk Kim, Wie-Soo Kang, Hyun-Jong Cho (2015) - PloS one
  16. SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway.
    Yu-Jeong Choi, Youn Kyung Choi, Kang Min Lee, Sung-Gook Cho, Soo-Yeon Kang, Seong-Gyu Ko (2016) - BMC complementary and alternative medicine
  17. Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis.
    Sa-Rang Oh, Seon Ok, Tae-Sung Jung, Sang-Ok Jeon, Ji-Min Park, Ji-Wook Jung, Deok-Seon Ryu (2017) - Asian Pacific journal of tropical medicine
  18. The Protective Effect of a Functional Food Consisting of
    Na-Ra Han, Hi-Joon Park, Seong-Gyu Ko, Phil-Dong Moon (2023) - Foods (Basel, Switzerland)
  19. Angelica gigasextract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction
    Geum-Hwa Lee, Hwa-Young Lee, Young-Je Lim, Ji-Hyun Kim, Su-Jin Jung (2023)
  20. Nodakenin Inhibits Melanogenesis Via the ERK/MSK1 Signaling Pathway.
    Yeahwa Yoon, Seunghee Bae, Tae Jin Kim, Sungkwan An, Jae Ho Lee (2023) - Die Pharmazie


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