Drynaria

Drynaria: A Comprehensive Reference

1. Identity and Botanical Classification

Nomenclature and Taxonomy

Drynaria is a genus of epiphytic ferns belonging to the family Polypodiaceae, order Polypodiales, class Polypodiopsida. The species Drynaria fortunei is a widely distributed medicinal plant with abundant resources. The pharmacopoeial drug is derived primarily from its rhizome. Drynaria roosii, commonly known as gu-sui-bu, is a species of basket fern of the family Polypodiaceae, native to Eastern Asia including eastern China, used in traditional Chinese medicine; this species is more frequently cited in Asian studies by its synonym Drynaria fortunei, though this is technically an illegitimate name.

The pharmacopoeial drug material is called Drynariae Rhizoma (also spelled Rhizoma Drynariae). In the Pharmacopoeia of the People's Republic of China, "Gusuibu" is limited to the dried rhizome of Drynaria roosii, which contains the active ingredient naringin (≥ 0.5% by dry weight).

A second widely studied species is Drynaria quercifolia (L.) J. Smith. It is commonly known as the oak leaf fern of the family Polypodiaceae, distributed widely in the evergreen forests of India and native to tropical areas of Africa, Asia, and Australia, where it is cultivated mostly as a medicinal plant. A third species, Drynaria rigidula, is an epiphytic medicinal plant used particularly in Indonesia. The rhizome of Drynaria rigidula has traditionally been claimed to have anti-infective properties.

Botanical Description

Drynaria roosii is an epiphytic (growing on trees) or epipetric (growing on rocks) plant. Like other species of Drynaria, it possesses two frond types — a fertile foliage frond and a sterile nest frond. Sterile nest fronds are rounded, shallowly-lobed, reddish-brown fronds overlapping each other; they bear no sori and form a "basket" characteristic of the genus. The fertile fronds are larger and deeply lobed, bearing one to three sori arranged on both sides of the central rib.

The authentic Drynaria fortunei rhizome is distinguished by its flat, elongated shape with dense soft brown scales, reddish-brown cross-section with yellow vascular bundles in a ring, and mild, slightly astringent taste. Drynaria fortunei (Kunze) J. Sm. is a perennial pteridophyte that belongs to the family Polypodiaceae.

Common Names and Synonyms

In Traditional Chinese Medicine (TCM), the rhizome is known as Gǔ Suì Bǔ (骨碎补), a name that literally translates as "mender of shattered bone." It is also known by the alternative names Hou Jiang (猴姜), Mao Jiang (毛姜), and Shen Jiang (申姜). Rhizoma Drynariae was first recorded in the classical text Ben Cao Shi Yi over 1,000 years ago.

Regional Species Variation

The Chinese Pharmacopoeia standard species is Drynaria fortunei (槲蕨). Common substitutes used regionally include Drynaria baronii (中华槲蕨, used in some southern provinces), Pseudodrynaria coronans (大叶骨碎补, Davalliaceae family, used in Guangxi and Guangdong), and Davallia species (海州骨碎补).

Common Dosage Forms and Preparations

Rhizoma Drynariae is the dried rhizome, or horizontal stem, of the Drynaria genus of ferns, most commonly Drynaria fortunei or Drynaria roosii. This plant part is recognized for its thick and fleshy appearance, often covered in dense, brown scales. The rhizome is prepared and consumed in multiple forms:

• Dried whole or sliced rhizome for decoction (water extraction/tea).
• Standardized extracts, particularly total flavonoid fractions (marketed as total flavonoids of Rhizoma Drynariae, TFRD), available as oral tablets or capsules for clinical use in China.
• External applications in which the rhizome is ground and mixed into a poultice or plaster that is applied directly to the skin over an injury.
• Liquid tinctures prepared with ethanol, vegetable glycerin, and water.
• Granule formulations used in compound herbal prescriptions.
• In many preparations, it is not used as a single herb but as part of a complex formula with other ingredients.

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2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

Rhizoma Drynariae was first recorded in Ben Cao Shi Yi over 1,000 years ago and is recognized as a "kidney-tonifying" herb for bone-related disorders such as osteoporosis and bone fracture for many years in China. It is an ancient Chinese herb that has been used in medicine for over a thousand years since the Tang Dynasty, extensively utilized in clinical practice — particularly in orthopedics — and commonly used to treat osteoporosis, non-union fractures, and joint diseases. It is believed to have the efficacy of tonifying the kidney and strengthening bones, as recorded in the classical text Sheng Hui Fang.

In TCM, Rhizoma Drynariae is primarily classified as a kidney "Yang" tonic, a category of herbs believed to address deficiencies related to the body's foundational energy and warmth. This classification informs its principal traditional use for strengthening bones and tendons. For generations, practitioners have used Gu Sui Bu to promote the healing of bone fractures and treat other traumatic injuries like sprains and ligament damage.

In the TCM paradigm, it warms and supports the Kidneys, which govern bone health, making it useful for lower back pain, loose teeth, tinnitus, and weak knees. It is also applied externally for patchy hair loss. Traditionally, it is used to strengthen bones and tendons and is also included in formulations for oral health, such as the treatment of loose teeth and bleeding gums. The rationale in traditional texts is based on the theory that strengthening the bones and "kidney essence" indirectly benefits the gums and teeth, since teeth are considered "the extension of bone" in traditional Chinese medical philosophy.

In the TCM materia medica classification system, Gu Sui Bu belongs to the categories of blood-invigorating and stasis-dispelling herbs (活血化瘀药) and blood-invigorating and trauma-healing herbs (活血疗伤药). It is frequently combined with Rehmannia glutinosa and Cornus officinalis when treating tinnitus and hearing loss due to kidney deficiency.

South and Southeast Asian Traditional Medicine

Drynaria quercifolia, a medicinal epiphytic fern of the Polypodiaceae family, has been an important component of traditional medicine systems across South and Southeast Asia. The rhizome has been utilized extensively in Ayurveda, Siddha, and folk medicine for treating bone fractures, inflammatory conditions, respiratory disorders, and gastrointestinal ailments.

In Maharashtra, India, the rhizome is ground into a paste and used to treat diarrhea, typhoid, cholera, chronic jaundice, fever, headache, and skin disease. In Bangladesh, D. quercifolia leaves and rhizome have been used by local inhabitants for the treatment of intestinal worms and abdominal pain. The fronds of Drynaria quercifolia have traditionally been used in rheumatic pain management.

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3. Key Chemical Constituents and Active Compounds

Overview of Phytochemical Classes

Recent phytochemical investigations have identified a diverse array of compounds in Drynariae rhizoma, including flavonoids, phenolic acids, lignans, and steroids. Among these, flavonoids represent the principal active constituents, attracting considerable research attention due to their extensive pharmacological activities.

Phytochemical analysis reveals the presence of bioactive compounds including flavonoids, phenolic acids, alkaloids, β-sitosterol, and triterpenoids. The preliminary phytochemical investigation of D. quercifolia showed the presence of alkaloids, glycosides, tannins, saponins, proteins and amino acids, flavonoids, triterpenes, phenols, phytosterols, and carbohydrates.

Principal Flavonoids

The major bioactive constituents of Rhizoma Drynariae are demonstrated to be flavonoids, among which naringin and neoeriocitrin are the two richest flavonoids. Naringin (a flavanone glycoside) is considered the primary marker compound and is specified in pharmacopoeial standards. Flavonoid naringin is widely distributed in various types of plants and is an important component of herbal Drynaria.

Isolation studies have yielded a new compound named drynaether A (1) and five known compounds including uracil, 4'-hydroxy-7-methoxyflavan, kaempferol, indole-3-carboxylic acid, and protocatechuic acid from methanol extract. Additional flavonoids identified across species include naringenin, neoeriocitrin, and multiple additional flavonoid glycosides. The 2025 comprehensive review in the Journal of Pharmacy and Pharmacology identified at least 60 distinct flavonoid components documented in the literature.

Other Significant Constituents

Various phytochemicals including 3,4-dihydroxybenzoic acid, friedelin, epifriedelinol, β-amyrin, β-sitosterol, and β-sitosterol 3-β-D-glucopyranoside have been isolated from D. quercifolia. A phytochemical study conducted on the rhizome of Drynaria rigidula successfully isolated two new aromatic glycosides as well as three known terpenoids, two benzoic acid derivatives, and two known flavonoid glycosides. The rhizome also contains polysaccharides; a homogeneous polysaccharide (DFPW) has been isolated and purified from the dried rhizome of Drynaria fortunei. Drynaria rhizome also contains the bioactive compound (−)-epicatechin.

In D. quercifolia, GC-MS analysis has identified a broad profile of volatile constituents. Detailed analysis of chromatograms has revealed the presence of 47 bioactive compounds in the methanolic rhizome extract of D. quercifolia, including squalene, n-hexadecanoic acid, and gamma-tocopherol, all of which possess anti-inflammatory activity.

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4. Established Mechanisms of Action

Osteogenic (Bone-Forming) Activity

The most thoroughly investigated mechanism is the promotion of bone formation. Naringin has been shown to increase osteoblast proliferation by increasing the expression of BMP-2, and to inhibit osteoclast activity by reducing the expression of RANKL. Drynariae fortunei extract hinders the formation of mature osteoclasts by modulating the expression of ALP, BMP2, Col1A1, and collagenase 1. Naringin increases the differentiation of mesenchymal stem cells (MSC) to osteoblasts by activating two signaling pathways: Wnt/β-catenin and BMP2.

Previous studies have demonstrated that the total flavonoids of Rhizoma Drynariae can partially activate the Wnt/β-catenin signaling pathway to promote bone graft mineralization and osteoblast differentiation in a dose-dependent manner. In vivo and in vitro experiments indicated that naringin activates the Wnt/β-catenin pathway and enhances the expression of Wnt3a and β-catenin proteins in OVX mice, thereby promoting osteogenesis.

Naringin can synergistically enhance the action of 1α,25-dihydroxyvitamin D3 in promoting the secretion of osteoprotegerin by osteoblasts in vitro. Naringin has antioxidant and free radical scavenging properties and can induce BMP-2 expression in osteoblasts, enhancing osteogenic differentiation and new bone formation.

Estrogenic / Phytoestrogenic Activity

Total flavonoids of Rhizoma Drynariae and naringin can mimic estrogen in stimulating cell proliferation and alkaline phosphatase (ALP) activity via activating estrogen receptor (ER) in rat osteoblastic UMR106 cells. The bone protective actions were mainly mediated by these flavonoid phytoestrogens via estrogen receptors, raising considerations about potential estrogen-like interactions when co-administered with other ER ligands, such as selective estrogen receptor modulators (SERMs).

Total flavonoids and isolated compounds stimulated the ratio of osteoprotegerin and receptor-activator NF-kB ligand (RANKL) mRNA expression, suggesting their involvement in inhibiting osteoclastogenesis. These stimulatory effects on osteoblastic functions were abolished in the presence of oestrogen receptor antagonist ICI 182780, suggesting the actions are mediated by ER.

Anti-Inflammatory Mechanisms

Experimental results have confirmed that naringin suppresses inflammation, including arthritis, by lowering the expression of inflammatory cytokines. The mechanism can be explained by the reduction of NF-κB expression. Naringin has also been shown to improve random skin flap survival and osteoporosis through promoting angiogenesis by regulating the VEGF/VEGFR signaling pathway and inhibiting inflammation by downregulation of TNF-α and IL-6.

Angiogenic Activity

Several key ingredients in D. fortunei are critical in influencing bone development; specifically, naringin has been reported to enhance osteoblast proliferation by augmenting the expression of BMP-2 and inhibiting osteoclast activity by reducing the expression of RANKL. Naringin has been found to enhance endothelial progenitor cell (EPC) proliferation and tube formation mediated by the activation of the PI3K/Akt signaling pathway via the CXCL12/CXCR4 axis.

Pyroptosis Inhibition (Bone Protection)

A 2024 study in ScienceDirect found a previously unreported mechanism. Rat serum ELISA, femoral tissue immunohistochemistry, and Western blot analysis showed that compared with the ovariectomized (OVX) group, Caspase-1, NLRP3, and GSDMD expression levels and inflammation were reduced (p<0.05), and the expression of osteogenic marker RUNX2 was increased (p<0.05), indicating that Gu Sui Bu inhibits bone loss via suppression of the NLRP3/GSDMD/Caspase-1 pyroptosis pathway.

Gut Microbiota Modulation

Research has established that total flavonoids of Rhizoma Drynariae (TFRD) can attenuate osteoporosis, with a clinical equivalent dose of 67.5 mg/kg/d identified as the effective dose for treating osteoporosis, and TFRD has been widely used in China for this purpose. Metagenomic and metabolomic analyses suggest that part of this activity may be mediated through the regulation of gut microbiota and related metabolites, though these mechanisms are still under active investigation.

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5. Scientific Evidence by Area of Use

5.1 Bone Health: Osteoporosis and Fracture Healing

Pre-Clinical Evidence (Animal and Cell Studies)

The bone-health evidence base is the most extensive for Drynaria. Flavonoid compounds are the main active constituents of Drynaria fortunei medicinal herb, and their biological activities include the promotion of fracture healing, prevention and treatment of osteoporosis, antioxidation, blood lipid regulation, anti-inflammation, and analgesia.

A homogeneous polysaccharide (DFPW) isolated and purified from the dried rhizome of D. fortunei was studied in ovariectomized (OVX) rats. Oral administration of DFPW at 100 mg/kg and 400 mg/kg for 12 weeks significantly improved trabecular bone mass, demonstrated by increases in trabecular area, trabecular thickness, and trabecular number in OVX rats. The OVX-induced decline in bone mineral density and bone mineral content, including Ca, P, and Mg, was reversed by DFPW administration.

The total flavonoid fraction (DFTF) exerted dose-dependent effects in improving bone mineral densities and bone strength at the femur, tibia, and lumbar spine L1 in OVX mice. DFTF and isolated compounds stimulated osteoblastic cell proliferation and alkaline phosphatase activities in a dose-dependent manner.

Naringin at concentrations of 0.1, 0.5, and 1 µmol/L significantly promoted osteoblast cell proliferation, enhanced ALP activity, and increased calcified nodule formation. Naringin also improved bone mineral density (BMD) and trabecular bone number in OVX mice. It elevated serum levels of bone formation markers (P1NP, OCN) while reducing the bone resorption marker CTX-1.

A study on bone graft in rat models found that naringin release testing showed that approximately 70 µg/mL of naringin could be released from scaffolds, and this amount was sufficient to induce BMSCs to differentiate into osteoblasts.

A study on TFRD combined with calcium carbonate found: total flavonoids of Rhizoma Drynariae treatment significantly improved bone microarchitecture and reversed histopathological damage in OVX mice.

Clinical / Human Evidence

A systematic review was performed to determine the clinical efficacy and safety of total flavonoids from Rhizoma Drynariae (TFRD) for osteoporotic fractures, searching eight databases to identify relevant randomized controlled trials (RCTs) until December 2016. Six RCTs involving 846 patients were included, with primary outcomes including fracture recurrence and death.

Meta-analysis showed that both combination therapy (TFRD plus conventional treatments) and TFRD alone were superior to conventional treatments in improving bone mineral density (BMD) value (WMD = 3.68; 95% CI: 0.01–0.04; P = 0.0002) and enhancing therapeutic effect (OR = 0.25; 95% CI: 0.12–0.51; P = 0.0002). Thirty-three patients experienced adverse drug reactions (ADRs); none of the ADRs were severe, and all were resolved after symptomatic treatments.

Evidence strength assessment: The systematic review and meta-analysis of six RCTs provides the strongest level of human evidence available for Drynaria. However, important limitations apply: all included trials were conducted in China, reporting quality was variable, and placebo-controlled blinded trials are limited. The evidence is promising but cannot yet be considered definitive by Western regulatory standards.

5.2 Hearing Protection (Ototoxicity)

A study investigated whether the flavonoid fraction (FF) from Drynaria fortunei has protective effects against gentamicin (GM) ototoxicity in guinea pigs (n = 36). Eleven animals received GM at 100 mg/kg/day. Eleven animals (GMFF group) received the same dose of GM, but were pre-dosed with FF (10 mg/kg/day) for 2 weeks starting 2 days prior to GM administration. The thresholds of tone-burst auditory evoked response (ABR) at 2 kHz, 8 kHz, and 32 kHz were measured; the GM group had ABR thresholds of 90 dB, 92 dB, and 72 dB, while the GMFF group had 30 dB, 37 dB, and 38 dB. The GM group had significantly higher hearing thresholds than all other groups (p < 0.05). The GMFF and FF groups had hearing thresholds similar to saline controls (p > 0.1).

Studies have shown that Drynaria fortunei can protect against the ototoxicity of aminoglycosides and streptomycin in guinea pig cochlear hair cells, thereby defending hearing. Gushen Pian, a herbal mixture consisting of Drynaria fortunei, Danshen (Salvia miltiorrhiza), licorice, and Calcined Ci Shi, was found to be effective in the treatment of sensorineural deafness and hearing loss.

Evidence strength assessment: Evidence for ototoxicity protection is limited to animal studies (guinea pig models) and one combination herbal formula. No controlled human clinical trials have been published specifically evaluating Drynaria alone for hearing protection. Evidence is preliminary.

5.3 Renal Protection (Nephroprotection)

The flavonoid fraction (FF) from Drynaria fortunei was investigated in three acute renal failure animal models. Guinea pigs received 100 mg/kg of gentamicin (GM group), 100 mg/kg of GM plus 10 mg/kg of FF (GMFF group), 10 mg/kg of FF (FF group), or saline for 14 days. Blood urea nitrogen (BUN) and creatinine levels were significantly higher in the GM group (22.70 ± 3.84 mg/dL; 0.68 ± 0.05 mg/dL) than in the GMFF group (17.10 ± 1.04 mg/dL; 0.58 ± 0.09 mg/dL) or FF group (17.40 ± 1.01 mg/dL; 0.49 ± 0.20 mg/dL).

In a mercuric chloride model, mice treated with HgCl2-saline had significantly higher BUN and creatinine than the HgCl2-FF group. In a 5/6-nephrectomy model, ten mice received FF at 10 mg/kg/day and eight received saline for 42 days; the saline group survived 12–62 days while the FF group survived 20–320 days, a significantly longer survival time (p < 0.05). Regeneration of kidney tubular cells and significantly enlarged convoluted tubules were noted in the FF group.

Evidence strength assessment: All renal protection evidence is from animal studies. No controlled human clinical trials have evaluated Drynaria for renal outcomes.

5.4 Anti-Inflammatory and Anti-Rheumatic Activity

Studies aimed at validating the traditional uses of D. quercifolia rhizome extracts in inflammatory conditions have used in vitro and in vivo approaches, identifying active constituents by GC-MS analysis and evaluating potential anti-inflammatory components against COX-2, TNF-α, and IL-6 via in silico molecular docking.

The fronds of D. quercifolia have traditionally been used in rheumatic pain management. To validate anti-inflammatory and anti-rheumatoid properties, methanolic extract was prepared from its rhizome. Protein denaturation tests and hemolysis assays were performed in vitro, and in vivo anti-rheumatoid potential was assessed in a Freund's complete adjuvant (FCA)-induced Wistar rat model through inflammatory paw-edema, haematological, biochemical, radiological, and histopathological measurements.

The study found that D. quercifolia rhizome extract exhibited a high percentage of protein denaturation inhibition, though slightly lower than the standard drug.

Evidence strength assessment: Anti-inflammatory evidence is primarily in vitro and animal-based. No human clinical trials focused specifically on inflammatory disease outcomes have been published. Evidence is preliminary.

5.5 Anti-Obesity Activity

Drynaria rhizome contains various bioactive compounds with capacity for alleviating obesity, such as (−)-epicatechin or naringin. Recent studies have focused on the complex relationship between bone health and obesity, including the effect of adipokines on bone cells and bone metabolism in type 2 diabetes.

A study investigated the effects of Drynaria rhizome extract (DRE) on high-fat diet (HFD)-induced obese mice, in which DRE was supplemented with the HFD. Body weight, food intake, and the expression levels of lipogenesis transcription factors including SREBP-1, PPAR-γ, and AMPK-α, as well as AMPK activation, were evaluated.

Evidence strength assessment: Anti-obesity evidence is limited to in vitro and rodent studies. No human clinical evidence exists. Evidence is preliminary and exploratory.

5.6 Anticancer / Antiproliferative Activity

The inhibitory effects of methanol, ethanol, and petroleum ether extracts of Drynaria fortunei on myeloma SP20 cells were tested at 12 h, 24 h, 36 h, and 48 h. The methanol and ethanol extracts had similar inhibition rates at 24 h, approximately 55%, while the maximum inhibition rate of petroleum ether extract was only 36% within 24 h.

In a triple-negative breast cancer (TNBC) model, the estrogen receptor-negative, progesterone receptor-negative MDA-MB-231 human breast carcinoma-derived cell line was used as the cellular model for TNBC. A non-fractionated aqueous extract from the bark of D. fortunei was used as the test agent. Treatment at cytostatic concentration induced S phase cell cycle arrest and inhibited RB signaling, as evidenced by the downregulated expression of cyclin E, CDK2, E2F1, and RB phosphorylation.

Evidence strength assessment: All anticancer evidence is from in vitro cell culture studies. No animal or human clinical studies evaluating cancer outcomes with Drynaria have been identified. This evidence is very preliminary.

5.7 Oral and Periodontal Health

A study investigated the management of grade II furcation defects in dogs using guided tissue regeneration (GTR) and D. fortunei granules mixed with β-tricalcium phosphate alloplast. Drynaria fortunei is a common type of traditional Chinese herb in the area of orthopedics and traumatology; in vitro and tissue engineering studies have shown that it induces osteoblastic proliferation and promotes the differentiation of human periodontal ligament cells.

Modern scientific research on Drynaria's effects specifically on gums is limited.

5.8 Acetylcholinesterase Inhibition

The serious side effects of licensed drugs used to treat Alzheimer's disease have forced researchers to investigate safer acetylcholinesterase (AChE) inhibitors from natural sources. Numerous plants and their constituents are reported in traditional medicine practices as AChE activity inhibitors to enhance cognitive function. Research published in PMC investigated Drynariae Rhizoma as a source of AChE inhibitors through bioguided isolation. Evidence is in vitro only and remains preliminary.

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6. Dosage Forms Reported in Scientific Studies

The following dosages are reported as used in cited published studies and do not represent clinical recommendations:

• In the gentamicin-induced acute renal failure animal study, guinea pigs received 10 mg/kg of the flavonoid fraction (FF) from Drynaria fortunei intramuscularly for 14 days.
• In the ototoxicity study, animals in the GMFF group received FF at 10 mg/kg/day for 2 weeks.
• Oral administration of DFPW polysaccharide at 100 mg/kg and 400 mg/kg for 12 weeks was evaluated in the OVX rat osteoporosis model.
• The clinical equivalent dose of TFRD identified in preclinical studies is 67.5 mg/kg/d as the effective dose for treating osteoporosis.
• In osteoblast culture studies, naringin concentrations of 0.1, 0.5, and 1 µmol/L were evaluated.

For human clinical use of the standardized TFRD extract, dosages used in the RCTs included in the systematic review were not individually detailed in the available abstract sources. No standardized human dosage has been established in Western pharmacopeial monographs.

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7. Safety Considerations and Interactions

General Toxicity Profile

It is reported in the published literature that Drynaria rhizome has no obvious toxic side effects. Nutritional herbs from TCM with limited reported toxicity have been considered as alternatives in areas of unmet need.

In the systematic review of six RCTs involving 846 patients, thirty-three patients experienced adverse drug reactions (ADRs); none of the ADRs were severe, and all were resolved after symptomatic treatments.

Estrogenic Activity and Potential SERM Interactions

This is the most clinically important documented interaction concern. The bone protective actions of Rhizoma Drynariae were mainly mediated by flavonoid phytoestrogens via estrogen receptors, raising concerns about its safety as it may induce an estrogen-like risk-benefit profile and potentially interact with other ER ligands, such as selective estrogen receptor modulators (SERMs), when co-administered. A study evaluated the estrogenic activities of RD and its potential interaction with tamoxifen, a SERM, in estrogen-sensitive tissues using mature ovariectomized rats and ER-positive cells.

Similar to, but weaker than, tamoxifen, RD at its clinical dose dramatically ameliorated OVX-induced changes in bone and dopamine metabolism-related markers in OVX rats. However, tamoxifen — but not RD — induced uterotrophic effects. No significant alteration in mammary gland was observed in OVX rats treated with RD, which was different from the inhibitory actions of tamoxifen.

The implication of this finding is that Drynaria may interact with co-administered estrogen receptor modulators, including tamoxifen used in breast cancer treatment, though this has been studied only in animal models to date.

Species Substitution Risk

Multiple fern species are used regionally as Gu Sui Bu substitutes, which can significantly affect therapeutic outcomes. The Chinese Pharmacopoeia standard species is Drynaria fortunei (槲蕨), while common substitutes include Drynaria baronii, Pseudodrynaria coronans, and various Davallia species. The phytochemical profiles, and therefore the biological activities and safety profiles, of these substitutes may differ from the standard species.

Antifertility Properties (D. quercifolia)

The rhizome of Drynaria quercifolia is reported in the preclinical literature to have anti-fertility, anti-inflammatory and antipyretic, antimicrobial, antioxidant, wound healing, and bone regenerative activity. The anti-fertility properties noted for D. quercifolia in the preclinical literature carry relevance to populations considering reproductive health.

Absence of Long-Term Human Safety Data

The currently available human clinical trial data for TFRD are limited to short-term studies, predominantly conducted in China, and no long-term (multi-year) controlled safety data comparable to those for established pharmacological bone therapies are available in the peer-reviewed Western literature.

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8. Summary of Evidence Strength

• Bone health / osteoporosis (Drynaria fortunei / TFRD): The strongest evidence base for this genus. Multiple in vitro, animal, and human RCT-level evidence exists. A published systematic review of six RCTs (n = 846) reports clinically meaningful improvements in BMD with an acceptable safety profile in the studied populations. Evidence is promising but predominantly from Chinese trials; independent replication and better trial design are needed.
• Hearing / ototoxicity protection: Supported by animal studies only. No human clinical trials available.
• Renal protection: Supported by animal studies only. No human clinical trials available.
• Anti-inflammatory / anti-rheumatic: Supported by in vitro and animal studies. No human clinical trials available.
• Anti-obesity: Supported by in vitro and mouse studies only.
• Anticancer: In vitro cell-line studies only. Highly preliminary.
• Oral / periodontal health: Very limited, primarily in vitro and animal models.

References

• Guo et al. (2025). A comprehensive review of Drynariae rhizoma: botany, traditional applications, and active flavonoid components. Journal of Pharmacy and Pharmacology, 77(10), 1319–1337.
• Zhang et al. (2017). Total flavonoids from Rhizoma Drynariae (Gusuibu) for treating osteoporotic fractures: implication in clinical practice. Drug Design, Development and Therapy, 11, 1881–1890. PMC5491704.
• Zhou et al. (2022). Water Extract of Rhizoma Drynaria Selectively Exerts Estrogenic Activities in Ovariectomized Rats and Estrogen Receptor-Positive Cells. Frontiers in Endocrinology. PMC8908013.
• Mukherjee et al. (2021). Validating potent anti-inflammatory and anti-rheumatoid properties of Drynaria quercifolia rhizome methanolic extract through in vitro, in vivo, in silico and GC-MS-based profiling. PMC7953762.
• A polysaccharide from the dried rhizome of Drynaria fortunei prevents ovariectomized (OVX)-induced osteoporosis in rats. PMC7131925.
• The Function of Naringin in Inducing Secretion of Osteoprotegerin and Inhibiting Formation of Osteoclasts. PMC4738947.
• A study of Drynaria fortunei in modulation of BMP-2 signalling by bone tissue engineering. PMC7491309.
• Drynaria fortunei Promoted Angiogenesis Associated With Modified MMP-2/TIMP-2 Balance and Activation of VEGF Ligand/Receptors Expression. PMC6160574.
• Naringin promotes osteoblast differentiation and ameliorates osteoporosis in ovariectomized mice. PMC11993710.
• Emerging Roles of Natural Compounds in Osteoporosis: Regulation, Molecular Mechanisms and Bone Regeneration. PMC11356869.
• On the Inhibitory Effect of Drynaria Fortunei Extract on Human Myeloma SP20 Cells. PMC3847433.
• Anti-proliferative effects of Drynaria fortunei in a model for triple negative breast cancer. PMC11650959.
• Drynaria rhizome water extract alleviates high-fat diet-induced obesity in mice. PMC10784730.
• Long et al. (2004). Flavanoid of Drynaria fortunei protects against gentamicin ototoxicity. Phytotherapy Research, 18, 609–614. PubMed PMID: 15476311.
• Long et al. (2005). Flavonoid of Drynaria fortunei protects against acute renal failure. Phytotherapy Research, 19, 422–427. PubMed PMID: 16106396.
• Research progress on Drynaria fortunei naringin on inflammation and bone activity. PubMed PMID: 25924506.
• Total Flavonoids of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane via Wnt/β-Catenin Signaling Pathway. PMC8188237.
• Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss via Wnt3a/β-catenin pathway. PMC8642843.
• Integrated metagenomic and metabolomic analyses of total flavonoids of Rhizoma Drynariae on osteoporosis via gut microbiota. PMC11828363.
• Gu Sui Bu (Drynaria fortunei J. Smith) prevents osteoporosis in ovariectomized rats by inhibiting pyroptosis through NLRP3/GSDMD/CASPASE-1. ScienceDirect (2024).
• Investigation of Phenolic Profiles, Cytotoxic Potential and Phytochemical Screening of Drynaria quercifolia (Leaves). PMC3848233.
• Ahmed et al. (2015). Drynaria quercifolia (L.) J. Smith (Polypodiaceae): phytoconstituents and ethnopharmacology. Pharmacologyonline, 1, 4–17.
• Drynaria fortunei-derived total flavonoid fraction and isolated compounds exert oestrogen-like protective effects in bone. British Journal of Nutrition (2013). Cambridge Core.
• Age-related hearing loss and its potential drug candidates: a systematic review. Chinese Medicine (2023). Springer Nature.
• Effects of Drynaria Total Flavonoid on the Microstructure of the Mandible in Ovariectomized Rats. PMC7640376.
• Drynaria roosii. Wikipedia (Aglaomorpha fortunei).
• Phytochemistry, Traditional Applications, and Therapeutic Properties of Drynaria quercifolia: Review Article. ResearchGate / Journal of Pharma Insights and Research (2025).
• Therapeutic potential of total flavonoids of Rhizoma Drynariae: inhibiting adipogenesis and promoting osteogenesis via MAPK/HIF-1α pathway. PubMed PMID: 40069718.