Hydrangea

The Cherokee used the bark of wild hydrangea. It was chewed for stomach trouble and for high blood pressure, and a bark infusion was given to induce vomiting “to throw off disordered bile” ^{30Reference 30Moerman DE · 1998Native American Ethnobotany — ethnobotanical referenceView study →}. A cold bark infusion was given to children to stop vomiting ^{30Reference 30Moerman DE · 1998Native American Ethnobotany — ethnobotanical referenceView study →}.

Scraped bark was applied as a poultice to burns, ulcers and swellings, and as a poultice for sprains and sore or swollen muscles ^{30Reference 30Moerman DE · 1998Native American Ethnobotany — ethnobotanical referenceView study →}. The inner bark and leaves were used as a stimulant, and a compound infusion was taken for menstrual periods ^{30Reference 30Moerman DE · 1998Native American Ethnobotany — ethnobotanical referenceView study →}.

The Cherokee also ate the plant. Peeled young twigs and branches were boiled into a tea, or cooked in grease like green beans ^{29,30Reference 29Freeman · 2016Hydrangea arborescens Linnaeus — species description, habitat and distribution — floraView study →Reference 30Moerman DE · 1998Native American Ethnobotany — ethnobotanical referenceView study →}.

The Delaware combined the root with the root of blue flag (Iris versicolor) for gallstones ^{30Reference 30Moerman DE · 1998Native American Ethnobotany — ethnobotanical referenceView study →}.

Eclectic physicians used the root as a soothing diuretic for the urinary tract ^{31,32Reference 31Felter HW · 1922Hydrangea — historical materia medicaView study →Reference 32Ellingwood F · 1919Hydrangea — historical materia medicaView study →}. Felter listed its specific indications as bladder and urethral irritation with gravel, difficult urination, deep-seated kidney pain, blood in the urine and irritation of the bronchial membranes ^{31Reference 31Felter HW · 1922Hydrangea — historical materia medicaView study →}.

Felter wrote that hydrangea does not dissolve gravel, but was believed to help prevent it from forming, especially alkaline and phosphate deposits ^{31Reference 31Felter HW · 1922Hydrangea — historical materia medicaView study →}. He recommended it in hot water, and for bladder irritation in the elderly ^{31Reference 31Felter HW · 1922Hydrangea — historical materia medicaView study →}.

Ellingwood used it for frequent, burning urination with sharp urethral pain, for pain from passing kidney sand, and for urinary irritation after childbirth ^{32Reference 32Ellingwood F · 1919Hydrangea — historical materia medicaView study →}. He often combined it with gelsemium, or with gelsemium and black cohosh ^{32Reference 32Ellingwood F · 1919Hydrangea — historical materia medicaView study →}. He recorded that trials around 1830 reported relief of pain from passing urinary stones ^{32Reference 32Ellingwood F · 1919Hydrangea — historical materia medicaView study →}.

A water extract of processed H. macrophylla leaf suppressed nitric oxide, PGE₂ and TNF-α in LPS-stimulated macrophages by inhibiting Akt-mediated NF-κB activation ^{1Reference 1Dilshara MG et al. · 2013In vitroWater extract of processed Hydrangea macrophylla leaf attenuates the expression of pro-inflammatory mediators by suppressing Akt-mediated NF-κB activation — in vitroView study →}. Isolated hydrangenol lowered nitric oxide and iNOS in LPS-stimulated BV2 microglia, by blocking NF-κB and activating the Nrf2/HO-1 pathway ^{2Reference 2Kim HJ et al. · 2016In vitroHydrangenol inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-mediated HO-1 pathway — in vitroView study →}.

In mice, oral hydrangenol (20 or 40 mg/kg) improved survival and reduced intestinal inflammation in LPS endotoxemia ^{3Reference 3Jang SY et al. · 2023AnimalProtective effect of hydrangenol on lipopolysaccharide-induced endotoxemia by suppressing intestinal inflammation — mouse in vivoView study →}. At 15 or 30 mg/kg it eased dextran-sulfate colitis, reducing macrophage infiltration and restoring tight-junction proteins ^{4Reference 4Kim SY et al. · 2023AnimalHydrangenol, an active constituent of Hydrangea serrata, ameliorates colitis by suppressing macrophage-mediated inflammation in DSS-treated mice — mouse in vivoView study →}.

A standardized hot-water extract of H. serrata leaves reduced inflammation and cartilage damage in macrophages, chondrocytes and two rodent arthritis models, through NF-κB and MAPK. Hydrangenol was identified as a major active compound ^{5Reference 5Heo HS et al. · 2025In vitroIn vitro and in vivo anti-inflammatory and chondroprotective effects of standardised hot-water extract from Hydrangea serrata via NF-κB and MAPK pathways — animal modelView study →}.

A synthetic hydrangenol derivative, more stable in plasma than hydrangenol, reduced paw inflammation and inflammatory pain in rats ^{6Reference 6Yoo HS et al. · 2025In vitroAnti-inflammatory and antinociceptive activities of a synthetic hydrangenol derivative — in vitro and in vivoView study →}.

Gap: no human anti-inflammatory data, and every positive study used a leaf extract or isolated hydrangenol, not an H. arborescens root decoction or tincture.

The antiallergic work comes mainly from the Yoshikawa and Matsuda group, using isocoumarins from Hydrangeae Dulcis Folium, the processed leaf of H. macrophylla var. thunbergii. Thunberginol A, B and F inhibited antigen- and calcium-ionophore-induced degranulation and the release of TNF-α and IL-4 in RBL-2H3 mast cells ^{10Reference 10Wang Q et al. · 2007In vitroInhibitory effects of thunberginols A, B and F on degranulation and release of TNF-α and IL-4 in RBL-2H3 cells — in vitroView study →}. Thunberginols A and B also suppressed AP-1 and ERK signalling, and thunberginol B’s gene-expression profile resembled that of the antiallergic flavone luteolin ^{11Reference 11Matsuda H et al. · 2008In vitroInhibitory effects of thunberginols A and B on cytokine mRNA expression and AP-1 activation in RBL-2H3 cells — in vitroView study →}.

Structure–activity work found the double bond at the 3-position essential for strong activity. This makes the thunberginols more potent than dihydro forms such as hydrangenol ^{9,10Reference 9Matsuda H et al. · 1999In vitroStructure requirements of isocoumarins, phthalides and stilbenes from Hydrangeae Dulcis Folium for inhibition of histamine release from rat peritoneal mast cells — in vitroView study →Reference 10Wang Q et al. · 2007In vitroInhibitory effects of thunberginols A, B and F on degranulation and release of TNF-α and IL-4 in RBL-2H3 cells — in vitroView study →}.

In the rat passive cutaneous anaphylaxis model, all the tested constituents except phyllodulcin significantly inhibited the reaction. Thunberginol A was the most potent, but the authors judged hydrangenol the main antiallergic component of the processed leaf once its higher content was taken into account ^{8Reference 8Matsuda H et al. · 1999AnimalEffects of phyllodulcin, hydrangenol, their 8-O-glucosides, and thunberginols A and F on passive cutaneous anaphylaxis reaction in rats — rat in vivoView study →}.

Thunberginols A, B and F were first isolated as combined antiallergic and antimicrobial principles ^{7Reference 7Yoshikawa M et al. · 1992In vitroThunberginols A, B, and F, new antiallergic and antimicrobial principles from Hydrangeae Dulcis Folium — in vitroView study →}.

Gap: the most potent compounds, the thunberginols, are documented only in the Asian processed leaf.

This indication has the only human trial. In a randomized, double-blind, placebo-controlled study, 151 participants took an H. serrata leaf extract (300 or 600 mg) or placebo once daily for 12 weeks ^{14Reference 14Myung DB et al. · 2020RCTOral intake of Hydrangea serrata leaves extract improves wrinkles, hydration, elasticity, texture and roughness in human skin: a randomised, double-blind, placebo-controlled study — randomised controlled trialView study →}. Both doses reduced skin wrinkles and roughness and improved hydration compared with placebo, and the 600 mg dose also improved elasticity. No extract-related adverse reactions were reported ^{14Reference 14Myung DB et al. · 2020RCTOral intake of Hydrangea serrata leaves extract improves wrinkles, hydration, elasticity, texture and roughness in human skin: a randomised, double-blind, placebo-controlled study — randomised controlled trialView study →}.

In UVB-irradiated human fibroblasts, hydrangenol preserved procollagen, raised hyaluronic-acid production and lowered MMP-1, MMP-3 and COX-2 expression ^{12Reference 12Shin JS et al. · 2019In vitroChemical constituents from leaves of Hydrangea serrata and their anti-photoaging effects on UVB-irradiated human fibroblasts — in vitroView study →}. In UVB-exposed hairless mice it reduced wrinkling and collagen loss, suppressed MAPK/AP-1 signalling and induced Nrf2/HO-1 ^{13Reference 13Myung DB et al. · 2019AnimalHydrangenol isolated from the leaves of Hydrangea serrata attenuates wrinkle formation and repairs skin moisture in UVB-irradiated hairless mice — mouse in vivoView study →}.

Gap: the trial tested a different species, a standardized oral leaf extract and a cosmetic endpoint, none of which relates to the urinary use of H. arborescens root.

Hydrangenol activates nuclear factor erythroid 2-related factor 2 (Nrf2), inducing heme oxygenase-1 (HO-1) and related protective genes in microglia and skin models ^{2,13Reference 2Kim HJ et al. · 2016In vitroHydrangenol inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-mediated HO-1 pathway — in vitroView study →Reference 13Myung DB et al. · 2019AnimalHydrangenol isolated from the leaves of Hydrangea serrata attenuates wrinkle formation and repairs skin moisture in UVB-irradiated hairless mice — mouse in vivoView study →}.

In Caenorhabditis elegans, a phyllodulcin-rich H. macrophylla leaf fraction raised catalase activity and lowered reactive oxygen species and fat accumulation under oxidative and heat stress ^{15Reference 15Cho M et al. · 2024AnimalPhyllodulcin from the hexane fraction of Hydrangea macrophylla inhibits glucose-induced lipid accumulation and ROS generation in Caenorhabditis elegans — in vivo (invertebrate)View study →}.

The work is preclinical, with no human biomarker data.

Hydrangenol, phyllodulcin, thunberginol A and hydrangeic acid from the processed leaf promoted fat-cell differentiation in 3T3-L1 cells. Hydrangenol and hydrangeic acid raised adiponectin, PPARγ2 and GLUT4 ^{16,17Reference 16Zhang H et al. · 2007In vitroNew type of anti-diabetic compounds from the processed leaves of Hydrangea macrophylla var. thunbergii — in vitro and mouseView study →Reference 17Zhang H et al. · 2009AnimalHydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound — KK-Aʸ mouse in vivoView study →}. Hydrangeic acid did not activate PPARγ directly, unlike the thiazolidinedione drugs ^{17,18Reference 17Zhang H et al. · 2009AnimalHydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound — KK-Aʸ mouse in vivoView study →Reference 18Matsuda H et al. · 2014ReviewSearch for a new type of PPARγ agonist-like anti-diabetic compounds from medicinal plants — reviewView study →}.

At 200 mg/kg/day for two weeks, hydrangenol lowered blood glucose and free fatty acids in diabetic KK-Aʸ mice ^{16Reference 16Zhang H et al. · 2007In vitroNew type of anti-diabetic compounds from the processed leaves of Hydrangea macrophylla var. thunbergii — in vitro and mouseView study →}, and hydrangeic acid lowered blood glucose, triglycerides and free fatty acids ^{17Reference 17Zhang H et al. · 2009AnimalHydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound — KK-Aʸ mouse in vivoView study →}.

In high-fat-diet mice, phyllodulcin (20 or 40 mg/kg/day for seven weeks) reduced subcutaneous fat and blood lipids and raised fat-browning genes (UCP1, PRDM16, PGC-1α) ^{19Reference 19Kim E et al. · 2017AnimalPhyllodulcin regulates obesity-related metabolic changes and fat-browning genes in high-fat-diet-induced obese mice — mouse in vivoView study →}. A 2026 study found hydrangenol disrupted fat-cell formation (AMPKα up; Akt/mTOR down) and shifted the gut microbiota in obese mice ^{20Reference 20Han HS et al. · 2026AnimalHydrangenol exerts anti-obesity effects by disturbing adipogenesis via mitotic clonal expansion and gut-microbiota dysbiosis — mouse in vivoView study →}.

Gap: rodent and cell work only, and phyllodulcin and hydrangeic acid have been documented only in the leaves of the Asian species.

Oral H. macrophylla extract protected cortical neurons against corticosterone toxicity and reduced restraint-stress anxiety in mice. Thunberginol C was identified as an active ingredient ^{21Reference 21Lee J et al. · 2022AnimalHydrangea macrophylla and thunberginol C attenuate stress-induced anxiety in mice — mouse in vivoView study →}.

Phyllodulcin inhibited amyloid-β aggregation, reduced hippocampal amyloid-β deposits and improved synaptic plasticity in 5XFAD Alzheimer’s-model mice ^{22Reference 22Cho E et al. · 2023AnimalPhyllodulcin improves hippocampal long-term potentiation in 5XFAD mice — mouse in vivoView study →}.

In vitro, thunberginol C and hydrangenol 8-O-glucoside pentaacetate inhibited both acetylcholinesterase and butyrylcholinesterase ^{23Reference 23Hwang J et al. · 2021In vitroDiscovery of natural inhibitors of cholinesterases from hydrangea (thunberginol C, hydrangenol 8-O-glucoside) — in vitroView study →}.

Each finding rests on a single preclinical study.

Hydrangenol inhibited the growth, migration and invasion of EJ bladder-cancer cells, through p21ᵂᴬᶠ¹-mediated G1 arrest, p38 MAPK activation and suppression of Sp-1-driven MMP-9, at an IC50 of 100 µM ^{24Reference 24Shin SS et al. · 2018In vitroHydrangenol inhibits proliferation, migration and invasion of EJ bladder cancer cells via p21ᵂᴬᶠ¹-mediated G1 arrest and p38 MAPK — in vitroView study →}.

A follow-up found hydrangenol inhibited VEGF-stimulated growth of human endothelial cells (EC50 10 µM), blocked VEGFR-2 signalling and MMP-2, and reduced vessel sprouting in an aortic-ring assay ^{25Reference 25Gho Y et al. · 2019In vitroHydrangenol suppresses VEGF-stimulated angiogenesis by targeting p27ᴷᴵᴾ¹-dependent G1 arrest and VEGFR-2 signalling — in vitroView study →}.

The work covers one cancer cell line plus in-vitro and ex-vivo angiogenesis models, with no animal tumour model.

The first isolation study described thunberginols A, B and F as combined antiallergic and antimicrobial compounds, active against oral bacteria ^{7Reference 7Yoshikawa M et al. · 1992In vitroThunberginols A, B, and F, new antiallergic and antimicrobial principles from Hydrangeae Dulcis Folium — in vitroView study →}.

A food-chemistry screen found that hydrangenol, phyllodulcin and naringenin from H. macrophylla var. thunbergii leaves bind the ACE2 receptor and inhibit SARS-CoV-2 spike–ACE2 binding in vitro ^{26Reference 26Yano A et al. · 2023In vitroDihydroisocoumarins of Hydrangea macrophylla var. thunbergii inhibit binding of the SARS-CoV-2 spike protein to ACE2 — in vitroView study →}.

The work is in vitro on isolated compounds, with no infection models.

Skin allergy. Hydrangea has caused occupational allergic contact dermatitis in a florist ^{28Reference 28Romita P et al. · 2020Case reportOccupational allergic contact dermatitis to Hydrangea spp. in an Italian florist — case reportView study →}.

Large doses. Traditional sources warn that large doses may cause dizziness, a feeling of tightness in the chest and stomach upset.

Cyanide. The root’s hydrangin is sometimes described as a cyanogenic glycoside. The name belongs to umbelliferone, a coumarin, which does not release cyanide ^{33Reference 33Malarz J et al. · 2024ReviewPolyphenols of the Inuleae-Inulinae and their biological activities: a review — reviewView study →}. A true cyanogenic glycoside, taxiphyllin, has been measured in the processed leaves of the Asian H. macrophylla var. thunbergii. Most of it breaks down during processing, and it was judged unlikely to have caused food-poisoning cases linked to the leaf tea ^{27Reference 27Tsukioka J et al. · 2023Quantitative analysis of taxiphyllin, a cyanogenic glycoside, in the leaves of Hydrangea macrophylla var. thunbergii — analyticalView study →}. It has not been studied in H. arborescens root.

Interactions. No herb–drug interaction studies exist for H. arborescens. Hydrangenol and hydrangeic acid from the Asian leaf lowered blood glucose in mice, which raises a theoretical additive effect with diabetes medicines; this has not been tested ^{16,17Reference 16Zhang H et al. · 2007In vitroNew type of anti-diabetic compounds from the processed leaves of Hydrangea macrophylla var. thunbergii — in vitro and mouseView study →Reference 17Zhang H et al. · 2009AnimalHydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound — KK-Aʸ mouse in vivoView study →}.