Hydrangea

Hydrangea as a Dietary Supplement and Medicinal Herb: A Comprehensive Reference

1. Identity, Taxonomy, and Botanical Overview

The genus Hydrangea is made up of over 70 plant species belonging to the family Hydrangeaceae. Of these, Hydrangea paniculata, Hydrangea macrophylla, and Hydrangea arborescens are the most prominent in terms of medicinal properties. H. paniculata and H. macrophylla are native to Asia, while H. arborescens is native to the eastern United States. A fourth species, Hydrangea serrata (Thunb.) Ser., grown primarily in Korea and Japan, has received growing research attention for its dermatological effects. Additionally, the related species Dichroa febrifuga (known as Chang Shan or Hydrangea febrifuga) is closely associated in East Asian medicine and shares key phytochemical constituents with the Hydrangea genus.

Common names for these species include hortensia, seven bark, wild hydrangea, smooth hydrangea, bigleaf hydrangea, and mophead hydrangea. The name Hydrangea is derived from a Greek word denoting a water vessel.

Medicinal Parts and Common Preparation Forms

Hydrangea root supplement is made from the plants' roots and underground stems, also known as the rhizomes. The hydrangea root (rhizome) is a small, grayish underground structure that contains many active ingredients. Hydrangea root supplements are available in various forms, including capsules, tinctures, powder, syrup, and liquid extracts. Traditional preparations also include decoctions (teas made from boiled root), fluid extracts, and infusions. In Japanese herbal practice, Hydrangea macrophylla var. thunbergii leaves are specifically fermented and dried — a preparation referred to in pharmacognosy as Hydrangeae Dulcis Folium — to produce a sweet tea used medicinally.

2. Traditional and Historical Use

Native American Traditions (North America)

The Cherokee Indians used Hydrangea to treat kidney and bladder stones, as did Traditional Chinese Medicine practitioners. According to Appalachian tradition, wild hydrangea is called "Seven Bark" for the peeling layers of bark revealing different colors. Some recorded uses include chewing the bark for stomach and heart troubles, though it has caused painful gastroenteritis and cyanide-like poisoning. The shrub is collected mainly for the root, juicy and tender, and used for kidney and bladder troubles.

These traditional medicines, with roots in Native American cultures that spread through folkloric American traditions, proliferated in pharmacies. Examples of these medicinal histories are preserved as "materia medica" in the National Museum of American History, labeled "crude drugs," and many were developed by the Eclectic School of American Practitioners (founded in the 1830s).

The Physicomedicalists of the 19th century used Hydrangea as part of a remedial formula in treating kidney disorders including nephritis. A historical 1885 publication in the medical literature noted that the value of this native plant in renal affections was first made known to the medical public by early American practitioners, and a preparation called "Lithiated Hydrangea" combined the active elements of the plant with lithia.

Traditional Chinese Medicine

Dichroa febrifuga is an important herb in traditional Chinese medicine, where it is considered one of the 50 fundamental herbs. Febrifugine, the bioactive constituent of one of the 50 fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity. The alkaloids febrifugine and isofebrifugine are believed to be responsible for its antimalarial effects. In traditional preparations, it is used in conjunction with other plants such as Glycyrrhiza glabra (licorice), Ziziphus jujuba, and Zingiber officinale (ginger).

Hydrangea paniculata Sieb is a medicinal herb widely distributed in southern China, and has been used to treat inflammation, malaria, and fever throughout Chinese history. The water extract of its branches and stems has been used in traditional Chinese practice to treat kidney diseases for extended periods.

Japanese Traditional Use

In order to develop new bioactive functions of Hydrangeae Dulcis Folium — the fermented and dried leaves of Hydrangea macrophylla Seringe var. thunbergii Makino — effects of the methanolic extract on antiulcer, antiallergic, cholagogic, and various pharmacological actions were investigated. The methanolic extract was found to exhibit potent antiulcer, antiallergic, and cholagogic activities. The fermented leaves are consumed in Japan as a sweet-tasting herbal tea, a practice historically connected to Buddhist temple rituals.

3. Key Phytochemical Constituents

The chemical profile of Hydrangea varies considerably by species, plant part, and preparation method. The following summarizes the principal classes of bioactive compounds identified in peer-reviewed phytochemical literature.

Dihydroisocoumarins and Isocoumarins

Hydrangenol is a dihydroisocoumarin regarded as one of the principal bioactive constituents across multiple Hydrangea species. Hydrangea plants have a variety of bioactive compounds such as dihydroisocoumarins, secoiridoids, and stilbenes (hydrangenol, phyllodulcin, macrophylloside, and their glucosides). Among these compounds, hydrangenol, a dihydroisocoumarin, has been reported to possess potential protective effects on cell viability, production of procollagen type I, MMP-1, and pro-inflammatory cytokines. Moreover, it has been reported that hydrangenol exhibits anti-inflammatory, anti-microbial, anti-diabetic, anti-allergic, antimalarial, and anti-cancer activities.

Phyllodulcin is another major dihydroisocoumarin found predominantly in the leaves of H. macrophylla. Among the bioactive compounds in Hydrangea macrophylla, phyllodulcin is a well-known non-sugar sweetener that is approximately 400 times sweeter than sucrose.

Among the newly isolated bioactive constituents from Hydrangeae Dulcis Folium — the fermented and dried leaves of Hydrangea macrophylla Seringe var. thunbergii Makino — eight antiallergic and antimicrobial principles were isolated together with several known compounds, including thunberginols A, B, and F. Thunberginols A, B, and F were found to exhibit more potent antiallergic activity than phyllodulcin, hydrangenol, disodium cromoglycate (DSCG), and tranilast, and also showed antimicrobial activity against oral bacteria.

Coumarins

Skimmin belongs to the coumarin family and is a common chemical compound present in many medicinal plants. It is also present in Hydrangea paniculata, accounting for approximately 55% of the total constituents in the water extract of its branches and stems. The most abundant coumarins in H. paniculata extract are skimmin (35.3%) and apiosylskimmin (18.9%), with other structure-known coumarins accounting for 25% of all ingredients. Total coumarins reach approximately 80% of the extract.

Compounds identified from the dried branches of H. paniculata include skimmin, isotachioside, an 8-methoxy coumarin glycoside, scopolin, a trimethoxybenzene rhamnosylglucoside, apiosylskimmin, umbelliferone, scopoletin, and 7-hydroxy-8-methoxycoumarin.

From the roots of Hydrangea chinensis, the quinazolone alkaloids (+)-febrifugine and isofebrifugine, along with the coumarin derivatives 6-hydroxy coumarin, skimmin, and umbelliferone-glucoside were isolated.

Quinazolone Alkaloids: Febrifugine and Isofebrifugine

The trans-2,3-disubstituted piperidine, quinazolinone-containing natural product febrifugine (also known as dichroine B) and its synthetic analogue, halofuginone, possess antimalarial activity. Febrifugine and isofebrifugine are constituents found in the roots of Hydrangea arborescens. These alkaloids are most concentrated in Dichroa febrifuga, the botanical species closely related to Hydrangea that serves as their primary natural source.

Flavonoids and Other Constituents

In Hydrangea arborescens, documented constituents include carbohydrates (gum, starch, sugars), flavonoids (kaempferol, quercetin, rutin), saponins, resin, and hydrangin (a glycoside). Additional constituents include alkaloids and antioxidants such as quercetin, saponins, and kaempferol, as well as various minerals including calcium, magnesium, zinc, and selenium.

A comprehensive phytochemical analysis of Hydrangea macrophylla var. acuminata leaves resulted in the isolation of 41 secondary metabolites, including four new compounds: one phenolic and three bis-iridoid glycosides.

Cyanogenic Glycosides

The flowers and leaves of Hydrangea have been claimed to cause toxicity in humans, potentially due to the cyanogenic glycoside, hydrangin, which is also found in the root. Hydrangeas contain naturally occurring compounds called cyanogenic glycosides, primarily amygdalin and hydrangin. When plant tissue is chewed or damaged, enzymes break these glycosides down and release hydrogen cyanide (HCN), a cellular toxin. This is an important safety consideration that distinguishes the toxicological profile of whole-plant parts from standardized root extracts used as supplements.

4. Mechanisms of Action

Hydrangenol: Collagen, Anti-Inflammatory, and Metabolic Effects

Hydrangenol, a principal constituent of Hydrangeae Dulcis Folium, significantly increased the amount of adiponectin released into the medium and mRNA levels of adiponectin, PPARγ2, and GLUT4, while it decreased the expression of IL-6 mRNA. Furthermore, hydrangenol significantly lowered blood glucose and free fatty acid levels in KK-Ay mice at a dose of 200 mg/kg/d over two weeks.

In cell and animal models, hot water extracts from Hydrangea serrata leaves recovered UVB-reduced cell viability and ameliorated oxidative stress by inhibiting intracellular reactive oxygen species (ROS) generation. The extract also rescued UVB-induced collagen degradation by suppressing MMP expression, and reduced the mRNA levels of inflammatory cytokines.

In vitro, synthetically derived hydrangenol has been shown to inhibit hyaluronidase activity and histamine release.

Febrifugine and Halofuginone: Aminoacyl-tRNA Synthetase Inhibition and Immune Modulation

Halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of TH17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. HF binds glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting prolyl-tRNA synthetase activity — an inhibition reversed by the addition of exogenous proline. Inhibition of EPRS underlies the broad bioactivities of this family of natural product derivatives.

Halofuginone has been reported to be a potent and selective inhibitor of Th17 differentiation, functioning by inducing a state of nutritional stress known as the amino acid starvation response. Treatment of naïve T cells with halofuginone was found to block Th17 differentiation and concomitantly increase Foxp3 expression without impacting cell proliferation, or Th1 or Th2 differentiation. Administration to mice selectively reduced both Th17 differentiation and the development of Th17-driven experimental autoimmune encephalomyelitis (EAE).

More recently, studies have also shown that halofuginone acts as an agent capable of reducing fibrosis, an indication with clinical relevance for several disease states.

Skimmin: Renal Protective Mechanisms

Skimmin has demonstrated renal protective activity in a rat model of streptozotocin-induced diabetic nephropathy. Skimmin treatment significantly decreased plasma creatinine, improved creatinine clearance, and reduced the incidence of glomerulosclerosis and tubulointerstitial injuries in animals following diabetic nephropathy induction.

In experimental membranous nephritis rats treated with H. paniculata coumarins for six weeks, deteriorated renal function and gut dysbiosis (as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness) were reversed by treatment.

Phyllodulcin: Metabolic Effects

Studies investigated whether phyllodulcin could improve metabolic abnormalities in high-fat diet (HFD)-induced obese mice. Animals were fed a 60% HFD for 6 weeks to induce obesity, followed by 7 weeks of supplementation with phyllodulcin (20 or 40 mg/kg body weight per day). Phyllodulcin supplementation reduced subcutaneous fat mass, levels of plasma lipids, triglycerides, total cholesterol, and LDL cholesterol, and improved levels of leptin, adiponectin, and fasting blood glucose. These are animal-model findings only and have not been confirmed in human clinical trials.

5. Scientific Evidence by Area of Use

5.1 Urinary Tract Conditions and Kidney Stone Prevention

Traditional claim: Traditionally, Hydrangea was used for urinary calculi with gravel and cystitis, urethritis, as a diuretic, and as an antilithic agent. Any action upon calculi was traditionally thought to be due to an eliminatory process rather than a dissolving function, meaning Hydrangea was seen to be effective against small stones only and of value in preventing their formation.

Scientific evidence: Hydrangea root has been used for hundreds of years to treat urinary conditions like prostate and bladder infections, enlarged prostate, and kidney and bladder stones. However, test-tube and animal research only back up its use as a possible way to protect kidneys from injury, and it is speculated that some of its plant compounds may provide anti-inflammatory and antioxidant activities. Human research on all of its purported benefits is lacking.

The body of evidence for the urinary/renal applications of H. paniculata coumarins is substantially more developed in preclinical models than for H. arborescens root. The current research has evaluated the renal protective effect of aqueous extract of H. paniculata by cisplatin-induced acute kidney injury (AKI) in animal models. Administration of H. paniculata could improve renal function by decreasing concentrations of blood urea nitrogen (BUN) and creatinine, and attenuated renal oxidative stress, tubular pathological injury, and apoptosis. All such studies are preclinical. No randomized controlled human clinical trials exist for hydrangea root in the treatment or prevention of kidney stones or urinary tract infections.

5.2 Skin Health (Anti-Aging, Photoprotection)

This is the area with the most direct human clinical evidence. Previously, researchers reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. A randomized, double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of WHS on human skin.

Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks.

A single toxicity test confirmed that WHS did not show any toxicity above 5,000 mg/kg. Based on a comprehensive review of the single toxicity test intake and the pharmacologically active dose, the daily intake was set at 300 mg/day and 600 mg/day, deemed safe for the human application test.

An additional clinical study using a topical formulation confirmed parallel findings: in clinical studies, skin wrinkles and skin moisturizing levels were improved in subjects applying 0.5% H. serrata hot water extract (Hs-WE) compared to the placebo group. The mechanistic basis was further investigated at the cellular level: repeated application of hydrangea extract produces anti-wrinkle effects by upregulating moisturizing factors and skin barrier constituents without skin toxicity.

Evidence strength: Moderate. There is one peer-reviewed, adequately powered RCT (n = 151) and supporting in vitro and animal data for the skin-aging application of H. serrata extract. These findings require replication by independent research groups and longer-term follow-up to establish durability. The evidence is species- and preparation-specific and cannot be generalized to H. arborescens root.

5.3 Renal Protection in Nephropathy Models

Multiple preclinical studies have examined the coumarin fraction of H. paniculata for kidney protection. Previous studies demonstrated that skimmin administration could slow the progression of streptozotocin-induced diabetic nephropathy and cationized BSA-induced membranous glomerulitis. Water and ethanol extracts of H. paniculata, a traditional Chinese medicinal plant, were used to test renoprotective effects in a lipopolysaccharide (LPS)-induced murine model of septic AKI.

A previous study demonstrated renal protective activity for skimmin in a rat model of streptozotocin-induced diabetic nephropathy. Skimmin treatment significantly decreased plasma creatinine, improved creatinine clearance, and reduced the incidence of glomerulosclerosis.

Evidence strength: Preclinical only (rodent models). No human clinical trials have been conducted specifically on skimmin or H. paniculata coumarin extracts for kidney disease in humans.

5.4 Anti-Diabetic and Metabolic Effects

Two 3-phenyldihydroisocoumarins (hydrangenol and phyllodulcin), a 3-phenylisocoumarin (thunberginol A), and a stilbene (hydrangeaic acid) from Hydrangeae Dulcis Folium promoted adipogenesis of 3T3-L1 cells. Hydrangenol significantly increased adiponectin, PPARγ2, and GLUT4 mRNA levels while decreasing IL-6 mRNA expression. Furthermore, hydrangenol significantly lowered blood glucose and free fatty acid levels after administration at 200 mg/kg/d in KK-Ay mice over two weeks.

The inhibitory activities of compounds from H. macrophylla var. acuminata against the diabetes-associated enzymes PTP1B and α-glucosidase were evaluated. One compound exhibited potent dual inhibition with IC50 values of 8.0 µM for PTP1B and 3.4 µM for α-glucosidase; others showed notable α-glucosidase inhibitory activity.

Evidence strength: Preliminary; in vitro and animal studies only. No human clinical trials have been completed on any Hydrangea species for the management of diabetes or metabolic syndrome.

5.5 Antimalarial Activity (Febrifugine/Halofuginone Lineage)

Halofuginone is a synthetic analogue of febrifugine, the active principal of the Chinese herb Chang Shan (Dichroa febrifuga), which has been used to treat fever and malaria for more than 2,000 years. Febrifugine itself causes severe emesis and gastrointestinal irritation, and in the 1960s a number of analogues — including halofuginone — were synthesized by U.S. Army scientists looking for novel antimalarials.

Febrifugine derivatives have been used to treat malaria, cancer, fibrosis, and inflammatory disease. Halofuginone (HF) is a synthetic halogenated derivative of febrifugine. The immunosuppressant properties of HF have been reported; this compound has been shown to inhibit T cell proliferation, human Th17 differentiation, and cytokine production in activated T cells. In preclinical models, treatment with HF reduces the severity of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, and delayed-type hypersensitivity responses.

Evidence strength: The natural compound febrifugine itself is not clinically used due to toxicity. The synthetic derivative halofuginone has undergone preclinical investigation and some early clinical trials for conditions including scleroderma, but has not gained regulatory approval for human therapeutic use. Research on febrifugine is scientifically significant primarily as the template for drug discovery rather than as a directly administered natural supplement.

5.6 Anti-Allergic Activity

The known lipophilic constituents phyllodulcin and hydrangenol have been found to show antiallergic activity on Schultz-Dale reactions in preclinical testing. The chemical structures of thunberginols A, B, and F were determined on the basis of chemical and physicochemical evidence, and were found to exhibit more potent antiallergic activity than phyllodulcin, hydrangenol, DSCG, and tranilast. These findings are from in vitro and animal studies, and no human clinical trials on anti-allergic effects of Hydrangea have been identified in the peer-reviewed literature.

5.7 Liver Protection

The chemical compounds like coumarins and secoiridoids in hydrangea extract were able to protect the liver from toxins in lab studies. These findings require additional supportive evidence through human studies. Hepatoprotective coumarin and secoiridoid constituents have been documented from H. paniculata in preclinical work, but no human clinical trials have been completed in this area.

6. Body Systems and Health Areas Associated with Hydrangea

• Urinary/Renal System: Historically the primary focus; diuretic and antilithic uses in H. arborescens; preclinical evidence of renal protection from coumarins of H. paniculata.
• Integumentary System (Skin): The most robust human clinical evidence concerns H. serrata leaf extract (hydrangenol) and anti-aging skin outcomes.
• Immune System: Febrifugine/halofuginone lineage shows Th17 cell inhibition and potential autoimmune modulation in preclinical models.
• Metabolic/Endocrine System: Hydrangenol, phyllodulcin, and hydrangeic acid demonstrate anti-diabetic activity in preclinical models; no human data.
• Hepatic System: Preclinical hepatoprotective data from coumarin fractions; no human clinical trials.
• Antimicrobial: Thunberginols demonstrated activity against oral bacteria in vitro.

7. Dosage Forms and Doses Reported in Research

The following dosages are reported as stated in cited sources and do not represent established therapeutic recommendations, as no human clinical dosing standards have been established by regulatory bodies for H. arborescens root.

• Dried root or decoction (H. arborescens), traditional/herbalist use: 6–12 g/day of dried root or by decoction.
• Tincture (1:5 in 40% ethanol), traditional herbalist use: 2–4 mL tincture three times a day.
• Oral H. serrata leaf extract (WHS), clinical trial (skin aging): Participants were assigned to receive either WHS 300 mg or WHS 600 mg, once daily for 12 weeks.
• Hydrangenol animal study (blood glucose): Hydrangenol significantly lowered blood glucose and free fatty acid levels after administration at a dose of 200 mg/kg/d in KK-Ay mice.
• Phyllodulcin (obesity/metabolic animal study): Animals were supplemented with phyllodulcin at 20 or 40 mg/kg body weight per day.
• Traditional Chinese use of Chang Shan (Dichroa febrifuga): A typical dosage for Chang Shan is 3–9 grams, generally fried in wine to reduce the plant's side effects, except when being used as an emetic.

8. Safety Considerations and Toxicology

Cyanogenic Glycoside Toxicity

Hydrangeas contain naturally occurring cyanogenic glycosides, primarily amygdalin and hydrangin. When plant tissue is chewed or damaged, enzymes break these glycosides down and release hydrogen cyanide (HCN), a cellular toxin. However, the concentration in hydrangeas is relatively low compared to classically cyanogenic plants like bitter almonds. The most common symptoms in animals or children that eat a few leaves are gastrointestinal, such as stomach pain, nausea, vomiting, and diarrhea. Complications with the central nervous system are typically only seen in large ingestions, and symptoms consist of lethargy, labored breathing, seizures, and coma.

The flowers and leaves have been claimed to cause toxicity in humans, potentially due to the cyanogenic glycoside hydrangin, which is also found in the root. The bark has caused painful gastroenteritis and cyanide-like poisoning in some reported cases.

Gastrointestinal Effects

Hydrangea has been reported to cause gastroenteritis. Information from older texts describes symptoms of overdose as dizziness, a feeling of constriction in the chest, and disorders of the central nervous system. Its use may cause side effects such as nausea, vomiting, upset stomach, and dizziness, and there is no established dosage for the supplement.

Contact Dermatitis

Hydrangea has been associated with contact dermatitis. The plant has minimal potential for sensitization due to the presence of hydrangenol as an allergen. Patients ingesting hydrangea may develop vomiting and epigastric discomfort soon after exposure. Allergic contact dermatitis due to the sensitizer hydrangenol has been reported. Some sensitive individuals, particularly florists and nursery workers with frequent exposure, may develop contact dermatitis from the plant's sap.

Febrifugine-Specific Toxicity

Febrifugine itself causes severe emesis and gastrointestinal irritation, which was a key factor driving the synthesis of analogues with lower toxicity. The high antimalarial activity of febrifugine was accompanied by gastrointestinal toxicity associated with, for example, diarrhea, vomiting, and liver toxicity. This profile limits the therapeutic use of the parent natural compound to traditional preparations in which it is typically co-administered with herbs believed to moderate its side effects.

Lack of Human Safety Data

Human research on all of the purported benefits of hydrangea root is lacking. The absence of rigorous human safety data means that the tolerance of long-term oral supplementation, drug-herb interactions, and effects in vulnerable populations (pregnancy, children, impaired renal function) have not been formally characterized in clinical studies.

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References

• Myung DB et al. "Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study." Nutrients, PMC, 2020.
• Lee et al. "Hydrangea serrata Hot Water Extract and Its Major Ingredient Hydrangenol Improve Skin Moisturization and Wrinkle Conditions via AP-1 and Akt/PI3K Pathway Upregulation." PMC, 2023.
• Park et al. "Hydrangea serrata (Thunb.) Ser. Extract Attenuate UVB-Induced Photoaging through MAPK/AP-1 Inactivation in Human Skin Fibroblasts and Hairless Mice." PMC, 2019.
• Zhang et al. "Skimmin, a Coumarin from Hydrangea paniculata, Slows down the Progression of Membranous Glomerulonephritis by Anti-Inflammatory Effects and Inhibiting Immune Complex Deposition." PMC, 2013.
• Sen et al. "Total Coumarins from Hydrangea paniculata Protect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis." PMC, 2017.
• Zhang et al. "Total Coumarins from Hydrangea paniculata Show Renal Protective Effects in Lipopolysaccharide-Induced Acute Kidney Injury via Anti-inflammatory and Antioxidant Activities." Frontiers in Pharmacology / PMC, 2017.
• Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota. PMC, 2023.
• Keller TL et al. "Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase." PubMed/Nature Chemical Biology, 2012.
• Zhu S et al. "The chemistry and biology of febrifugine and halofuginone." PubMed/Bioorganic & Medicinal Chemistry Letters, 2014.
• Arooj M et al. "Halofuginone — The Multifaceted Molecule." PMC, 2018.
• Ma Y et al. "Halofuginone Synergistically Enhances Anti-Proliferation of Rapamycin in T Cells and Reduces Cytotoxicity of Cyclosporine in Cultured Renal Tubular Epithelial Cells." PMC, 2015.
• Cheng JJ et al. "Chemical constituents from Hydrangea chinensis." PubMed, 2003.
• Wang ZB et al. "Chemical constituents from Hydrangea paniculata." PubMed/Zhongguo Zhong Yao Za Zhi, 2011.
• Yoshikawa M et al. "Development of bioactive functions in Hydrangeae Dulcis Folium. III. On the antiallergic and antimicrobial principles — Thunberginols A, B, and F." PubMed, 1995.
• Phytochemical constituents of Hydrangea macrophylla var. acuminata leaves and their inhibitory activity against PTP1B and α-glucosidase. PMC, 2025.
• Morikawa T et al. "New type of anti-diabetic compounds from the processed leaves of Hydrangea macrophylla var. thunbergii." ScienceDirect/Bioorganic & Medicinal Chemistry Letters, 2007.
• Febrifugine — an overview. ScienceDirect Topics.
• Hydrangea arborescens Monograph. Southern Cross University Medicinal Plant Garden.
• Selected Hydrangea Histories. Smithsonian National Museum of Natural History.
• Hydrangea Root: Supplements, Uses, and Benefits. Healthline (evidence-based review), 2021.
• Toxicology Answer: Take Care with the Bigleaf Hydrangea. ACEP Now, 2022.
• The Hydrangea Arborescens (historical medical article, 1885). PMC/NLM Historical Collection.
• Phyllodulcin from the hexane fraction of Hydrangea macrophylla inhibits glucose-induced lipid accumulation and reactive oxygen species generation in Caenorhabditis elegans. PubMed, 2024.