An evidence-focused review of Tu Si Zi (Cuscutae Semen), its pharmacological activities, and its relevance to botanical ingredient development.

At a Glance

Cuscuta seed is a traditional Chinese medicinal ingredient with an expanding preclinical research base. Its flavonoids, polysaccharides, and other constituents have been investigated in reproductive, antioxidant, bone, and metabolic research.

 

 

Research relevant to sperm health includes sperm motility, sperm concentration, testicular structure, mitochondrial function, and the blood–testis barrier. Most of the evidence discussed here comes from cell and animal studies.

Cuscuta is commonly paired with goji berry, Cistanche, dong quai, Achyranthes root, and Atractylodes macrocephala rhizome. Each pairing has a different traditional rationale and research focus.

For Cistanche suppliers and supplement developers, the Cuscuta–Cistanche combination is a research-led formulation opportunity-not a clinically established fertility intervention. Much of the cited evidence concerns multi-herb formulas rather than the isolated two-herb combination.

Extract identity, manufacturing consistency, safety, and human validation matter more than pathway diagrams alone. Network pharmacology and molecular docking generate hypotheses; they do not establish clinical efficacy.

Evidence and terminology note: This article reviews traditional uses, computational predictions, laboratory experiments, animal studies, and selected clinical reports. These evidence types are not interchangeable. Traditional Chinese medicine concepts such as "Kidney," "Liver," "Spleen," "essence," and "yin–yang" describe a traditional theoretical framework and should not be equated directly with modern anatomical organs or biomedical diagnoses. Historical use to "support pregnancy" does not establish safety during pregnancy.

 

Abstract

Cuscuta seed, known as Tu Si Zi or Cuscutae Semen, is a commonly used Kidney-tonifying medicinal material in traditional Chinese medicine. Experimental research has investigated its reproductive-protective, antioxidant, antitumor, and other pharmacological activities. It is frequently combined with goji berry (Lycii Fructus), dong quai (Angelicae Sinensis Radix), Cistanche (Cistanches Herba), and other medicinal materials in traditional herbal pairings intended to provide complementary effects.

This review summarizes the pharmacological activities of Cuscuta seed and the reported applications and mechanisms of its commonly used herbal pairings. It also examines findings from modern network pharmacology alongside experimental and clinical research. Particular attention is given to the relationship between traditional compatibility theory, proposed biological mechanisms, and the limitations of the available evidence.

The review provides a reference for further research, ingredient development, and responsible evaluation of Cuscuta seed and its herbal combinations.

Keywords: Cuscutae Semen; Cuscuta seed; Tu Si Zi; pharmacological activity; herbal pairing; herbal compatibility; reproductive health; research progress

 

Introduction: What Is Cuscuta Seed?

Cuscutae Semen consists of the dried mature seeds of Cuscuta australis R.Br. or Cuscuta chinensis Lam., plants belonging to the family Convolvulaceae.[1] Commonly known as Tu Si Zi in Chinese and Cuscuta seed or dodder seed in English, it has also been associated with traditional names such as Tu Si Zi, Tu Si Shi, Wu Gen Teng, and Dou Ji Sheng.

Cuscuta plants parasitize a range of herbaceous hosts, including plants traditionally classified within Fabaceae, Asteraceae, and Chenopodiaceae. They occur throughout China, with major producing regions including Liaoning, Jilin, Hebei, Henan, Shandong, and Jiangsu.

Cuscuta seed was first recorded in the Shen Nong Ben Cao Jing, where it was classified as a superior-grade medicinal material.[2] In traditional Chinese medicine, it is described as neutral in nature and pungent and sweet in taste, with an affinity for the Liver, Kidney, and Spleen meridians.

Its traditional functions include:

Nourishing the Liver and Kidney.

Securing essence and reducing excessive urination.

Supporting pregnancy.

Supporting vision.

Relieving diarrhea.

Modern pharmacological reviews describe flavonoids, polysaccharides, alkaloids, steroids, amino acids, and trace elements among its constituents. Experimental studies have investigated reproductive protection, bone protection, antitumor activity, and antioxidant effects.[3]

What Are Herbal Pairings?

A herbal pairing, sometimes translated as a "drug pair," combines two medicinal materials according to traditional compatibility principles. Such pairings are intended to enhance desired effects, complement one another, or reduce unwanted effects.[4]

As relatively stable, small-scale building blocks of multi-herb prescriptions, herbal pairings have long been important in traditional Chinese medicine. Cuscuta seed is used both alone and in combination with other medicinal materials. These combinations provide a basis for investigating how composition, preparation, and relative proportions may influence biological activity.

This review summarizes the pharmacology of Cuscuta seed and research on its commonly used pairings, providing a framework for further compatibility studies and ingredient development.

1. Pharmacological Activities of Cuscuta Seed

1.1 Reproductive Protection

1.1.1 Male Reproductive Protection

Protection against experimentally induced reproductive toxicity

Xia Huifang and colleagues investigated an aqueous Cuscuta seed extract in male mice exposed to cyclophosphamide.[5] The extract counteracted several indicators of reproductive toxicity.

Reported changes included:

Increased thickness of the spermatogenic epithelium.

Increased numbers of spermatogenic cells and testicular interstitial cells.

Greater numbers of spermatocytes, spermatids, and spermatozoa within the seminiferous tubules.

Improved sperm motility and concentration.

A lower proportion of morphologically abnormal sperm.

These findings support further investigation of Cuscuta seed in reproductive injury models, but they do not establish benefits for men taking a commercial supplement.

Leydig cell protection and apoptosis-related proteins

Li Lijuan and colleagues reported that total Cuscuta flavonoids promoted the proliferation of mouse Leydig cells and reduced acrolein-induced cell injury and apoptosis.[6]

The authors proposed that the anti-apoptotic effects were associated with:

Increased expression of B-cell lymphoma 2 protein, or Bcl-2.

Decreased expression of Bcl-2-associated X protein, or Bax.

Decreased expression of caspase-3.

Leydig cells are involved in testosterone production, making their survival and function relevant endpoints in male reproductive research.

Oxidative stress and the Nrf2/HO-1 pathway

Guo Shilei and colleagues investigated Cuscuta flavonoids in a rat model of varicocele.[7] They proposed that the flavonoids protected spermatogenic function by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway, commonly abbreviated as Nrf2/HO-1.

The reported mechanism involved increased expression of Nrf2 and its downstream target HO-1 in testicular tissue, with corresponding reductions in oxidative stress-related injury and apoptosis.

Protection in bisphenol A exposure models

Tao Jinliang and colleagues reported that Cuscuta flavonoids increased testosterone and luteinizing hormone levels in their experimental investigation and significantly improved the survival of mouse Leydig cells injured by bisphenol A, or BPA.[8]

These findings suggest a protective effect under the conditions studied. They should not be interpreted as proof that Cuscuta seed increases testosterone in healthy men.

1.1.2 Female Reproductive Protection

Estrogen-like activity

Sun Xiangming and colleagues identified nine constituents associated with the estrogen-like activity of Cuscuta seed.[9] These included hyperoside, astragalin, a methylated quercetin glucuronide, quercetin, and kaempferol.

The study investigated direct-acting constituents responsible for estrogen-like effects and reported responses in ovariectomized rats, using diethylstilbestrol as a comparator.

Estrogen-like activity is relevant to both efficacy research and safety assessment. It does not, by itself, demonstrate suitability for people with hormone-sensitive conditions.

Follicular development and ovarian reserve

Follicular growth and development are important indicators of ovarian function.

Zhang Yan and colleagues found that mice receiving Cuscuta polysaccharides by oral administration showed increased development of follicles at different stages compared with other study groups.[10] The findings suggested an improvement in ovarian reserve-related measures.

The researchers also reported changes in splenic regulatory T cells, or Tregs. Reduced levels of CD4⁺CD25⁺ Tregs were associated with delayed ovarian functional decline in the model studied. These results concern model-specific immune changes and should not be generalized into a recommendation to suppress Tregs.

Protection against reproductive effects of prenatal BPA exposure

Liu Ying and colleagues reported that Cuscuta flavonoids reduced reproductive injury in adult female offspring following maternal BPA exposure during pregnancy.[11]

The proposed mechanism involved activation of Nrf2/HO-1 signaling and increased messenger RNA expression of:

HO-1.

Nrf2.

NAD(P)H quinone oxidoreductase 1, or NQO1.

These changes were associated with reduced oxidative stress.

Research on premature ovarian insufficiency

Xie Ying and colleagues combined network pharmacology, molecular docking, and animal experiments to investigate Cuscuta seed in premature ovarian failure, a term used in the cited literature that overlaps with the current clinical terminology of premature ovarian insufficiency.[12]

Their analysis identified a multi-component, multi-target, and multi-pathway profile. Constituents such as quercetin, kaempferol, and sesamin were associated with targets including:

Tumor protein p53, or TP53.

AKT serine/threonine kinase 1, or AKT1.

SRC tyrosine kinase.

Tumor necrosis factor, or TNF.

Epidermal growth factor receptor, or EGFR.

Enriched pathways included the database category "lipid and atherosclerosis," while associated biological processes included wound healing and responses to oxidative stress and reactive oxygen species.

The accompanying animal work supported further investigation of these mechanisms. However, pathway enrichment does not establish that every predicted compound–target relationship occurs in vivo.

Polycystic ovary syndrome research

Zhao Qianying and colleagues reported that total Cuscuta flavonoids improved thyroid hormone and sex hormone measures, reduced insulin resistance, and promoted ovulation in a rat model of polycystic ovary syndrome, or PCOS.[13]

They proposed mechanisms involving:

Inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase signaling, or MAPK/ERK.

Activation of follicle-stimulating hormone–cyclic adenosine monophosphate/protein kinase A signaling, or FSH–cAMP/PKA, in ovarian granulosa cells.

These are preclinical findings rather than established clinical outcomes in women with PCOS.

1.2 Bone Protection

Postmenopausal osteoporosis models

Meng Zhuoran and colleagues used ovariectomized rats to model postmenopausal osteoporosis.[14] Oral administration of an ethanol extract of Cuscuta seed was reported to:

Increase bone mineral density.

Reduce bone histopathological changes.

Decrease trabecular separation.

The proposed mechanism involved downregulation of microRNA-21-5p, or miR-21-5p, with increased expression of Fas ligand, or FasL.

Osteoarthritis and inflammatory signaling

Zhang Tiandong and colleagues used network pharmacology and molecular docking to identify 11 potential active constituents of Cuscuta seed, including sesamin and quercetin, together with 12 core overlapping targets associated with osteoarthritis.[15]

Enrichment analysis identified several pathways, including nuclear factor kappa B, or NF-κB, signaling.

Experimental validation indicated that sesamin reduced interleukin-1β-induced inflammatory injury in chondrocytes by inhibiting NF-κB signaling and lowering cyclooxygenase-2 expression.

Bone healing in osteoporotic fractures

Liang Chen reported that an aqueous Cuscuta seed extract increased the expression of several bone growth-related proteins in rats with osteoporotic fractures.[16] These included:

Bone morphogenetic protein 2, or BMP-2.

Transforming growth factor beta, or TGF-β.

Insulin-like growth factor 1, or IGF-1.

Vascular endothelial growth factor, or VEGF.

The study reported improved bone-healing outcomes in the animal model.

Osteoblast survival

Sun Qihua and colleagues found that Cuscuta flavonoids increased expression of the long noncoding RNA ZBED3-AS1, reduced p21 and caspase-3 levels, and inhibited TNF-α-induced osteoblast apoptosis.[17]

The intervention also promoted osteoblast proliferation under the experimental conditions studied.

1.3 Antitumor Research

Important distinction: The studies in this section concern experimental anticancer activity. They do not establish Cuscuta seed as a cancer treatment or justify cancer prevention or treatment claims for food supplements.

Inhibition of cancer cell proliferation

Ye Chunlin and colleagues reported that Cuscuta polysaccharides inhibited the proliferation of:

Human lung adenocarcinoma A549 cells.

Human liver cancer HepG2 cells.

Human pancreatic cancer PANC-1 cells.

The reported inhibitory effect on normal-cell proliferation was comparatively smaller under the tested conditions.[18]

Pancreatic inflammation–cancer transition

Xiao Xiang and Wu Xuanyu used gene-expression data mining and bioinformatics to identify genes involved in the transition from pancreatic inflammation to cancer and to predict potentially relevant Chinese medicinal materials.[19]

The original review linked Cuscuta seed and its constituents with potential multi-target, multi-pathway activity in this context. This was a predictive analysis, not evidence of established treatment effects in pancreatitis or pancreatic cancer.

Breast cancer models and PI3K/AKT signaling

Song Hui and colleagues combined network pharmacology, molecular docking, and animal experiments to investigate an ethanol extract of Cuscuta seed in breast cancer models.[20]

Their results suggested modulation of the phosphatidylinositol 3-kinase/protein kinase B pathway, or PI3K/AKT, with:

Reduced phosphorylated PI3K.

Reduced phosphorylated AKT.

Reduced Bcl-2 expression.

Increased Bax expression.

An increased Bax/Bcl-2 ratio.

These changes were associated with increased tumor-cell apoptosis in the mouse model.

Liver cancer cell apoptosis

Using microfluidic chip technology, Sun Yue and colleagues investigated the compatibility of pharmacologically active fractions from Compound Muji Granules.[21] Cuscuta flavonoids were identified as one of the principal fractions associated with apoptosis in HepG2 cells.

Because this work concerned fractions within a compound formulation, the findings should be interpreted within that formulation and experimental context.

PTEN, PI3K, and VEGF-related mechanisms

Zheng Yibo and colleagues investigated the effects of total Cuscuta flavonoids on the PI3K/PTEN/VEGF signaling axis in HepG2 cells.[22]

They reported increased expression of phosphatase and tensin homolog, or PTEN, a tumor-suppressor protein. PTEN dephosphorylates phosphatidylinositol 3,4,5-trisphosphate, or PIP3, converting it to phosphatidylinositol 4,5-bisphosphate, or PIP2, thereby reducing signaling that supports AKT activation.

The proposed downstream consequences included reduced tumor-cell and endothelial-cell proliferation, migration, invasion, and angiogenesis.

1.4 Antioxidant Activity

Polysaccharides and free-radical scavenging

The reviewed literature reports that Cuscuta polysaccharides have reducing activity and can scavenge several free radicals in laboratory assays, including:

2,2-Diphenyl-1-picrylhydrazyl radicals, commonly abbreviated as DPPH.

Hydroxyl radicals.

Superoxide anion radicals.

Total flavonoid extraction and activity

Qin Jingjing and colleagues extracted total flavonoids from Cuscuta seed using reflux extraction and optimized the process with a Box–Behnken design.[23]

In vitro testing showed scavenging activity against DPPH, hydroxyl, and superoxide anion radicals, supporting antioxidant activity under the assay conditions.

These chemical assays are useful for screening and process comparison, but they do not directly measure clinical antioxidant benefits after oral consumption.

Animal research and a citation inconsistency

The supplied review attributes to Liu Haiyun and colleagues increases in serum IL-13 and TNF-α, increased superoxide dismutase activity, reduced malondialdehyde levels, improved resistance to oxidative stress, and improvement in insomnia-related symptoms.[24]

However, the listed title of reference [24] concerns learning and memory and ATPase activity in liver and brain tissues of naturally aging mice, rather than an insomnia study. The attribution and specific outcomes therefore require verification against the original paper.

Chromatographic fingerprints and spectrum–effect relationships

Wu Xiaoying and colleagues established ultra-performance liquid chromatography, or UPLC, fingerprints for 11 Cuscuta seed extracts.[25]

They assessed in vitro antioxidant activity with DPPH and ABTS assays and examined relationships between chromatographic peaks and antioxidant performance using:

Orthogonal partial least squares analysis.

Grey relational analysis.

Four chromatographic peaks were positively associated with antioxidant activity. The authors proposed that multiple constituents contributed jointly to the observed effects.

For extract developers, this type of spectrum–effect analysis may help connect chemical consistency with laboratory activity, although it is not a substitute for human efficacy testing.

1.5 Other Investigated Activities

Pregnancy-Related Immune Regulation

Chen Xuemei and colleagues studied total Cuscuta flavonoids applied at the Sanyinjiao acupoint in a rat miscarriage model.[26]

The study reported effects on pregnancy outcomes and T-helper 1/T-helper 2 cytokine balance. The supplied review describes an increased ratio of T-box transcription factor T-bet to GATA-binding protein 3, or GATA-3, alongside improved maternal–fetal immune tolerance.

The direction and interpretation of these immune changes should be checked against the original study. The findings also concern a specific acupoint application method and cannot be assumed to apply to orally consumed extracts.

Insulin Resistance and Glucose Regulation

Wang Zhigang and colleagues used network pharmacology and molecular docking to investigate potential mechanisms by which Cuscuta seed might affect insulin resistance.[27]

Their analysis identified 121 pathways, including:

TNF signaling.

Hypoxia-inducible factor 1, or HIF-1, signaling.

Toll-like receptor signaling.

PI3K/AKT signaling.

Potential targets included JUN, AKT1, TP53, RELA, MAPK1, and TNF.

These results provide hypotheses for experimental investigation; they do not establish blood glucose control in humans.

Exercise-Related Fatigue

Zhang Dongqiang and Liu Zhixin investigated purification of Cuscuta polyphenols using macroporous resin and obtained a polyphenol purity of 62.2%.[28]

In mice, the preparation was reported to:

Extend pole-climbing time.

Reduce post-exercise serum lactate.

Reduce serum urea nitrogen.

Increase glutathione peroxidase activity.

Reduce malondialdehyde formation.

The authors interpreted these findings as evidence of activity against exercise-related fatigue in the animal model.

Cognitive Function

Zhao Qian and colleagues investigated Cuscuta seed in a rat model of Alzheimer's disease.[29]

The study associated improvements in cognitive impairment with changes in glycogen synthase kinase-3 beta, or GSK-3β, signaling, regulation of related proteins, improved neuronal function, and reduced excessive neuronal apoptosis.

Chronic Diarrhea

Lei Wei and colleagues reported that Cuscuta seed improved several measures in young rats with chronic diarrhea.[30]

Reported effects included:

Reduced stool output.

A lower proportion of wet feces.

Improved colonic mucosal structure.

Reduced serum D-xylose and inflammatory markers.

Changes in the intestinal microbiota.

These findings were associated with improvement in diarrhea-related symptoms in the model.

Topical Application in Herpes Zoster

The supplied review also describes reformulation of a traditional Cuscuta preparation into a cream. It states that a clinical investigation found shorter times to complete crust formation and pain resolution in patients with herpes zoster.

No corresponding reference was supplied for this statement. It should therefore be treated as an unverified report rather than an established clinical finding.

 

2. Cuscuta Seed Herbal Pairings: Pharmacology and Reported Applications

2.1 Cuscuta Seed and Goji Berry

Traditional pairing: Cuscutae Semen–Lycii Fructus
Common names: Tu Si Zi and Gou Qi Zi

Traditional Rationale

The original review traces the Cuscuta–goji pairing to the Tang-dynasty text Dao Jiao Xuan Jie Lu and its association with Wuzi Yanzong Wan, a formula traditionally praised for supporting reproductive function.

In traditional theory, Cuscuta seed nourishes the Liver and Kidney while supporting yang, whereas goji berry nourishes Liver and Kidney yin.

The combination is intended to reflect mutual support between yin and yang: yang is sustained by yin, while yin is replenished through yang's transforming activity. Together, the herbs are used to nourish Kidney essence.

This is a traditional explanatory framework, not a demonstrated biomedical mechanism.

Sperm Quality and Testicular Structure

Zhao Cong and colleagues studied the pairing in mice with oligoasthenozoospermia induced by Tripterygium glycosides.[31]

Oligoasthenozoospermia refers to a combination of reduced sperm concentration and reduced sperm motility.

The researchers reported increases in:

Testicular weight.

Sperm concentration.

Total sperm motility, expressed as progressive plus non-progressive motility, or PR + NP.

They proposed that these improvements were associated with reduced structural injury to the testes.

Mitochondrial Protection and Germ-Cell Survival

Wang Jisheng and colleagues investigated serum obtained from animals administered the herbal pairing.[32] This "medicated serum" approach is used in some laboratory studies to expose cells to circulating substances following administration.

The serum was reported to:

Improve mitochondrial membrane potential.

Reduce mitochondrial and other organelle damage.

Repair ultrastructural injury induced by Tripterygium glycosides.

Inhibit apoptosis in spermatogenic cells.

These findings are relevant to mitochondrial and cell-survival research, but the experimental exposure is not equivalent to giving the herbal combination directly to humans.

PI3K/AKT Signaling

Bao Binghao and colleagues reported improved spermatogenic cell function and proposed involvement of PI3K/AKT-related proteins.[33]

Deng Sheng and colleagues subsequently reported that the Cuscuta–goji pairing increased protein and messenger RNA expression of PI3K, AKT, and Bcl-2 in a rat model.[34]

These changes were associated with:

Increased cell proliferation.

Reduced apoptosis.

Improved testicular tissue structure.

Increased sperm concentration and motility.

Premature Ovarian Insufficiency

Zong Zheng and colleagues combined UPLC–quadrupole time-of-flight mass spectrometry, or UPLC-Q-TOF-MS, with network pharmacology to investigate the pairing in relation to premature ovarian insufficiency.[35]

Key constituents included:

Hyperoside.

Kaempferol.

Quercetin.

Isoquercitrin.

Ferulic acid.

Associated pathways included PI3K/AKT, neuroactive ligand–receptor interactions, and MAPK signaling. Enriched functions and processes included protein serine/threonine/tyrosine kinase activity, membrane rafts, and responses to peptides.

Li Jinying and colleagues also used network pharmacology to investigate the pairing in premature ovarian failure.[36] They identified potential roles for PI3K/AKT signaling and targets such as AKT1, TP53, and CASP3.

Associated biological processes included:

Positive regulation of transcription from RNA polymerase II promoters.

Signal transduction.

Oxidation–reduction processes.

Inflammatory responses.

Cell proliferation.

Apoptosis.

These findings remain largely mechanistic predictions.

Blood–Testis Barrier Integrity

Guan Siqi and colleagues found that the Cuscuta–goji pairing increased expression of proteins involved in testicular cell junctions in rats with impaired spermatogenesis.[37]

These included:

Occludin.

Zonula occludens-1, or ZO-1.

Connexin 43.

The reported changes were associated with restoration of blood–testis barrier integrity and improved spermatogenic function.

2.2 Cuscuta Seed and Cistanche

Traditional pairing: Cuscutae Semen–Cistanches Herba
Common names: Tu Si Zi and Rou Cong Rong

Traditional Rationale

The supplied review identifies the Cuscuta–Cistanche combination in historical formulas such as Roucongrong Wan from Yi Xin Fang and Tusizi Wan from Sheng Ji Zong Lu.

In traditional terms, the combination is used to:

Tonify the Kidney.

Support yang.

Replenish essence and marrow.

Modified Congrong Tusizi Wan, described in modern Chinese gynecological therapeutics, is traditionally used to nourish essence and blood and regulate the Chong and Ren vessels.

These concepts provide the historical rationale for the pairing but do not establish modern clinical efficacy.

Mitochondrial Function and Ovarian Research

Shi Wei, Liu Min, and colleagues investigated Xinjia Congrong Tusizi Decoction in several studies.[38–41] This is a multi-herb formula containing Cistanche and Cuscuta seed, not simply a two-ingredient preparation.

The studies explored several related mechanisms.

SIRT1/PGC-1α signaling and mitochondrial biogenesis

The formula was reported to influence the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway, or SIRT1/PGC-1α.

Associated changes included increased expression of:

Nuclear respiratory factor 1, or NRF-1.

Mitochondrial transcription factor A, or TFAM.

These factors are involved in mitochondrial biogenesis and function.

p53/Nrf2 signaling and ferroptosis

Other work investigated p53/Nrf2 signaling and proteins associated with antioxidant defense and ferroptosis regulation, including Nrf2 and the cystine/glutamate transporter component SLC7A11.[38]

Ferroptosis is a form of regulated cell death associated with iron-dependent lipid peroxidation.

The formula was reported to reduce oxidative injury and ferroptosis-related changes in ovarian granulosa cells.

Mitochondrial structure, dynamics, and reproductive aging

Across the cited studies, reported outcomes included:

Improved mitochondrial morphology.

Improved mitochondrial energy metabolism.

Reduced oxidative stress.

Changes in mitochondrial dynamics.

Improved sex hormone measures.

Promotion of follicular growth and development.

Improvement in ovarian reserve-related endpoints in experimental models.

One study specifically investigated AMPK/SIRT1 signaling in rats with diminished ovarian reserve.[41]

Taken together, these studies provide a research basis for further work on the formula. They do not establish that Cistanche and Cuscuta alone reproduce the effects, or that a commercial combination delays reproductive aging in humans.

Clinical Experience Reports

Professor Wu Keming's clinical approach emphasizes treating the underlying pattern and regulating menstruation, with Kidney nourishment and replenishment of essence as central principles.

A published clinical experience report described the use of Xinjia Congrong Tusizi Pills in patients with premature ovarian failure, including successful pregnancy outcomes.[42] Such reports can generate hypotheses but do not provide the same level of evidence as controlled clinical trials.

Liu Xianhui and colleagues reported seven cases involving modified Da Tusizi Decoction for aplastic anemia complicated by femoral head necrosis.[43]

The review describes improvements in symptoms such as:

Aversion to cold and cold extremities.

Lower-back and knee weakness.

Hip pain.

Restricted lower-limb movement.

This was a small case series involving a multi-herb prescription. It cannot establish the efficacy of the isolated Cuscuta–Cistanche pairing.

2.3 Cuscuta Seed and Dong Quai

Traditional pairing: Cuscutae Semen–Angelicae Sinensis Radix
Common names: Tu Si Zi and Dang Gui

Traditional Rationale

Dong quai is traditionally described as warm in nature and sweet and pungent in taste, with an affinity for the Heart, Spleen, and Liver meridians.

Its traditional functions include:

Nourishing and moving blood.

Regulating menstruation.

Relieving pain.

Moistening the intestines and promoting bowel movements.

It has historically been praised as an important medicinal material for blood-related disorders.

Cuscuta seed is associated with the Liver, Kidney, and Spleen meridians. Under the traditional concept that the Liver and Kidney share a common source, the two herbs are combined to strengthen nourishment of essence and blood.

Prescription-Pattern Research in PCOS

A data-mining study of prescriptions used by experienced gynecological practitioners identified Cuscuta seed and dong quai as a frequently used combination in PCOS management.[44]

Frequency of use documents prescribing patterns; it does not demonstrate clinical effectiveness.

Predicted Mechanisms in PCOS

Wang Cuicui and Ma Xiaoxin used network pharmacology to investigate the pairing.[45] Potential pathways included:

Advanced glycation end product–receptor for advanced glycation end product signaling, or AGE–RAGE.

Fluid shear stress and atherosclerosis.

Endocrine resistance.

Potential targets included AKT1, MAPK1, IL-6, and estrogen receptor 1, or ESR1.

Yuan Renzhi and colleagues identified 22 core targets shared by the pairing and PCOS-related datasets.[46] These included:

Progesterone receptor, or PGR.

Androgen receptor, or AR.

Peroxisome proliferator-activated receptor gamma, or PPARG.

Nitric oxide synthase 3, or NOS3.

ESR1.

ESR2.

The analysis identified 36 principal enriched pathways, including HIF-1, TNF, and NOD-like receptor signaling.

The authors proposed possible roles in inflammatory regulation, lipid metabolism, microcirculation, and insulin resistance, alongside other predicted activities. These remain hypotheses generated from network analysis.

Formula-Based Clinical Research in Ovarian Insufficiency

Professor Zhang Yuzhen developed Zigui Yijing Decoction based on a traditional approach described as nourishing Tian Gui and restoring declining reproductive function.

The cited clinical study investigated Zishen Yutai Pills combined with Zigui Yijing Decoction in premature ovarian insufficiency.[47]

Reported changes included:

Reduced serum follicle-stimulating hormone, or FSH.

Reduced luteinizing hormone, or LH.

Increased estradiol, or E2.

Increased anti-Müllerian hormone, or AMH.

Improvements in uterine and ovarian measurements.

Increased endometrial thickness.

Increased antral follicle count, or AFC.

Because the intervention combined multi-herb formulations, these results cannot be attributed specifically to Cuscuta seed, dong quai, or their isolated pairing.

2.4 Cuscuta Seed and Achyranthes Root

Traditional pairing: Cuscutae Semen–Achyranthis Bidentatae Radix
Common names: Tu Si Zi and Niu Xi

Traditional Rationale

Achyranthes root is traditionally described as bitter and sour in taste and neutral in nature, with an affinity for the Liver and Kidney meridians.

Its traditional functions include:

Nourishing the Liver and Kidney.

Strengthening sinews and bones.

Moving blood and promoting menstrual flow.

Directing blood downward.

In the pairing, Achyranthes root is intended to complement the nourishing properties of Cuscuta seed while promoting movement, so that supplementation does not lead to stagnation.

Traditional descriptions also contrast the ascending, yang-supporting character of Cuscuta with the downward-directing action of Achyranthes. Together, the pair is used to nourish the Kidney and promote blood movement.

Sperm Mitochondrial Function and Semen Parameters

Professor Sun Zixue describes Kidney deficiency and collateral obstruction as a central traditional pattern in some patients with oligoasthenozoospermia.

His Yishen Tongluo Formula was designed to nourish the Kidney, replenish essence, activate blood, and unblock the collaterals.

Clinical studies of the formula reported:[48,49]

Increased DJ-1 protein expression.

Reduced reactive oxygen species.

Increased mitochondrial membrane potential.

Improved sperm quality.

Increased sperm concentration and total sperm count.

Increased percentages of progressively motile sperm.

Increased total motility, expressed as PR + NP.

These findings concern the complete formula rather than the isolated Cuscuta–Achyranthes pair.

Hypertensive Kidney Injury

Xu Jin and colleagues used network pharmacology to investigate the pairing in hypertensive kidney injury.[50]

Enriched pathways included:

Pathways in cancer.

AGE–RAGE signaling.

Lipid and atherosclerosis.

TNF signaling.

IL-17 signaling.

Potential targets included TP53, AKT1, RELA, MAPK1, TNF, MAPK14, and IL6.

The authors proposed that modulation of inflammatory responses might contribute to potential protective activity. The analysis did not establish clinical kidney protection.

A Chronic Kidney Failure Case Report

A report by Professor Qu Wei described the use of Shenshuai Mixture in one patient with stage 5 chronic kidney disease.[51]

The traditional treatment approach focused on strengthening the Spleen, nourishing the Kidney, activating blood, and resolving turbidity.

A single case report cannot establish efficacy or justify replacing standard nephrology care.

2.5 Cuscuta Seed and Atractylodes Macrocephala

Traditional pairing: Cuscutae Semen–Atractylodis Macrocephalae Rhizoma
Common names: Tu Si Zi and Bai Zhu

Traditional Rationale

Atractylodes macrocephala rhizome is traditionally described as sweet and bitter in taste and warm in nature, with an affinity for the Spleen and Stomach meridians.

Its traditional functions include:

Strengthening the Spleen and supporting qi.

Drying dampness.

Promoting fluid metabolism.

Reducing excessive sweating.

Supporting pregnancy.

Traditional theory describes the Kidney as the foundation of inherited constitution and the Spleen as the foundation of acquired nourishment.

Within this framework, Atractylodes supports the production of nourishment and blood, complementing Cuscuta's role in replenishing essence. Cuscuta, in turn, is intended to support the constitutional basis of Spleen and Stomach function.

Prescription Patterns in Recurrent Pregnancy Loss

Li Hemei and colleagues used association-rule analysis to examine prescriptions for recurrent spontaneous abortion.[52]

Cuscuta seed and Atractylodes were among the three most frequently used medicinal materials, and their pairing was commonly identified.

Modified Shoutai Wan is a representative formula discussed in this context.

Threatened Miscarriage Research

Liu Yuanyuan investigated modified Shoutai Wan in patients with early threatened miscarriage classified as having a Kidney-deficiency pattern.[53]

The study reported changes in:

Serum beta-human chorionic gonadotropin, or β-hCG.

IL-2.

TNF-α.

Vaginal bleeding.

Pregnancy outcomes.

These results concern a modified multi-herb formula, not a standalone Cuscuta–Atractylodes supplement.

Ferroptosis-Related Mechanisms

Han Han and colleagues investigated modified Shoutai Wan in patients with PCOS and early threatened miscarriage, focusing on ferroptosis-related mechanisms.[54]

Reported molecular changes included:

Increased glutathione peroxidase 4, or GPX4, gene expression.

Increased SLC7A11 gene expression.

Reduced transferrin receptor 1, or TFR1, gene expression.

The study associated these changes with reduced lipid peroxidation, reduced iron deposition, and inhibition of ferroptosis-related processes.

Reported clinical and hormonal outcomes included changes in β-hCG, estradiol, progesterone, pregnancy outcomes, and a higher rate of spontaneous delivery.

The study design, sample size, comparators, and safety reporting should be reviewed before drawing conclusions or considering any practical application.

Network Pharmacology in PCOS

Fan Cailian and Xu Chuanhua used network pharmacology to investigate the Atractylodes–Cuscuta pairing in PCOS.[55]

Their analysis suggested a multi-target, multi-pathway profile, with AKT1 identified as a key target.

This provides a starting point for experimental research rather than proof of clinical benefit.

 

3. Overall Conclusions and Research Gaps

Cuscuta seed is a widely used Kidney-tonifying medicinal material in traditional Chinese medicine. Its traditional functions include nourishing the Liver and Kidney, securing essence, reducing excessive urination, supporting pregnancy and vision, and relieving diarrhea.

Modern research has investigated constituents and fractions such as:

Hyperoside.

Cuscuta polysaccharides.

Cuscuta flavonoids.

Quercetin.

Other phenolic and non-phenolic constituents.

Across the studies reviewed, recurring molecular targets include AKT, TP53, MAPK1, and TNF. Frequently discussed pathways include PI3K/AKT and database-defined pathways such as "lipid and atherosclerosis."

The biological processes most often investigated involve:

Oxidative stress.

Inflammatory responses.

Apoptosis.

Mitochondrial function.

Cell proliferation and survival.

Experimental outcomes span reproductive protection, bone protection, antioxidant activity, antitumor effects, pregnancy-related immune regulation, glucose metabolism, and cognition.

However, these findings arise from different preparations, doses, models, and evidence types. They should not be combined into a single claim that Cuscuta seed has all of these effects in humans.

Why Compatibility Research Matters

Herbal compatibility is central to traditional Chinese medicine. Medicinal materials are combined according to the clinical presentation and their traditional properties, with the intention of improving effects or reducing unwanted responses.

For Cuscuta seed, combinations with goji berry, Cistanche, dong quai, Achyranthes root, and Atractylodes represent established traditional approaches worthy of further study.

Nevertheless, traditional compatibility does not automatically demonstrate pharmacological synergy.

To establish synergy, research must show that a combination performs differently from what would be expected from its individual components under an appropriate experimental model.

Ratios, Composition, and Pharmacokinetics Remain Understudied

The supplied review identifies the relative proportions of paired herbs as an important research gap.

Questions requiring further investigation include:

Do different ratios change the chemical profile of a combined preparation?

Does co-extraction alter constituent recovery or stability?

Do the biological mechanisms change with the ratio?

Are effects additive, synergistic, antagonistic, or simply dominated by one ingredient?

Does combining the herbs change absorption, distribution, metabolism, or elimination?

Are observed benefits reproducible across different batches and manufacturing processes?

Network pharmacology has created new opportunities to connect traditional formulations with molecular biology, genomics, transcriptomics, and proteomics.

Its strongest use is as part of a broader evidence program that includes chemical characterization, experimental validation, pharmacokinetics, toxicology, and appropriately designed human studies.

This review therefore provides a research framework rather than a definitive clinical guide.

 

4. What This Research Means for Cistanche Suppliers and Supplement Developers

The following section is an editorial application of the reviewed evidence, added for ingredient manufacturers, brand owners, and product-development teams. It is not part of the original review.

 

4.1 Match the Ingredient to a Specific Research Question

"Reproductive health" is too broad to function as a single development endpoint.

 

Cistanche Benefits

 High extraction ratio cistanche extract

Click To Visit The Listing Of Cistanche For Improving Male Manapause

 

 

 

A program focused on sperm motility should distinguish among:

Progressive motility.

Total motility.

Sperm concentration.

Total sperm count.

Morphology.

Sperm DNA integrity.

Pregnancy-related outcomes.

Improvements in one measure do not guarantee improvements in the others. Changes in semen parameters also do not automatically establish improved pregnancy or live-birth outcomes.

Similarly, ovarian reserve research, testosterone research, libido research, and general vitality research represent different development objectives.

4.2 Compare the Pairings Without Overstating Them

Pairing	Main research themes in this review	Principal evidence limitation
Cuscuta + goji berry	Sperm parameters, testicular structure, mitochondrial function, PI3K/AKT signaling, blood–testis barrier	Predominantly cell and animal studies; human efficacy remains insufficiently established here
Cuscuta + Cistanche	Traditional essence support; ovarian mitochondrial function, oxidative stress, and ferroptosis in containing formulas	Much of the evidence concerns multi-herb formulas, not the isolated pair
Cuscuta + dong quai	PCOS-related target predictions and formula-based ovarian insufficiency research	Network predictions and multi-formula interventions limit attribution
Cuscuta + Achyranthes	Formula-based semen and mitochondrial outcomes; kidney-injury pathway predictions	The isolated pair is not established by the cited formula studies
Cuscuta + Atractylodes	Pregnancy-related prescribing patterns, modified Shoutai Wan research, PCOS predictions	Pregnancy safety and pair-specific efficacy cannot be inferred

For a business developing a sperm-motility concept, the Cuscuta–goji literature in this review offers the most directly relevant preclinical endpoints among the pairings discussed.

 

 

For a Cistanche manufacturer, the Cuscuta–Cistanche literature provides a rationale for further investigation, particularly around mitochondrial biology. It does not yet support presenting the pairing as a proven male fertility formula.

4.3 Specify the Raw Material Before Specifying the Marketing Message

The terms "Cuscuta extract" and "Cistanche extract" are not complete technical specifications.

A useful ingredient dossier should identify:

The botanical species.

The plant part.

Geographic origin and traceability.

Authentication methods.

Extraction solvent and process.

Drug-to-extract ratio or equivalent manufacturing information.

Carrier materials and excipients.

Analytical methods and marker specifications.

Chromatographic fingerprints where appropriate.

Relevant contaminant and microbiological limits.

Stability data.

For Cuscuta seed, the source review recognizes Cuscuta australis and Cuscuta chinensis. These should not be treated as interchangeable without supporting quality and comparability data.

For Cistanche, the commercial species must likewise be identified explicitly. An extract of Cistanche deserticola should not automatically be assumed equivalent to an extract of Cistanche tubulosa.

4.4 Distinguish Quality Markers From Proven Active Doses

Cuscuta research often discusses flavonoids, polysaccharides, hyperoside, and quercetin. Cistanche ingredient specifications may include phenylethanoid glycosides such as echinacoside and acteoside.

These measurements can be useful for identity, process control, and batch consistency.

However:

A higher marker concentration does not necessarily mean a better reproductive-health outcome.

A marker is not automatically the sole active constituent.

A standardized extract is not automatically equivalent to the extract used in a published study.

A raw-herb dose cannot be converted into an effective extract dose solely from a marketing extract ratio.

A credible specification should connect the manufactured ingredient to the preparation actually studied wherever possible.

4.5 Treat the Combination Ratio as an Experimental Variable

The reviewed literature does not establish an optimal Cuscuta–Cistanche ratio for sperm motility or reproductive health.

A defensible development program would compare:

Cuscuta alone.

Cistanche alone.

Several defined combination ratios.

A relevant control.

Consistent total exposure across comparison groups.

It should also distinguish between:

Blending separately manufactured extracts.

Co-extracting the two raw materials.

Combining powders.

Using a larger multi-herb formula.

These are different products and may have different chemistry, stability, and biological activity.

4.6 Build an Evidence Ladder

A practical research sequence could include:

Step 1: Identity and quality

Confirm botanical authenticity, contaminant control, chemical consistency, and stability.

Step 2: Fit-for-purpose laboratory testing

Select assays relevant to the intended mechanism rather than relying only on generic antioxidant screening.

Step 3: Safety and exposure assessment

Evaluate available toxicology, potential interactions, hormonal activity, and the suitability of the proposed population.

Step 4: Human feasibility research

Use a clearly specified finished formulation, appropriate eligibility criteria, predefined endpoints, and systematic adverse-event monitoring.

Step 5: Controlled clinical validation

Test the actual commercial formulation with suitable comparators, adequate duration, and clinically meaningful outcomes.

A mechanistic finding should be treated as one rung on this ladder-not as a replacement for the entire program.

4.7 Keep US and European Marketing Claims Separate From Research Discussion

A scientific review may describe animal models of infertility, PCOS, or ovarian insufficiency. That does not mean a supplement containing the ingredient can legally be marketed to treat those conditions.

For the United States, proposed structure/function claims require appropriate substantiation and compliance with applicable labeling and notification rules. Disease-treatment claims create different regulatory issues.

For the European Union, ingredient eligibility, novel-food considerations, national botanical rules, and health-claim requirements must be checked for the specific species, plant part, extract, and destination market. Botanical claim rules and transitional provisions are complex; traditional use alone should not be treated as blanket authorization.

The United Kingdom should also be assessed separately rather than assumed to follow every current EU requirement.

A disclaimer does not make an otherwise misleading or unauthorized claim acceptable. Product pages, educational articles, testimonials, metadata, and linked sales content should be reviewed together.

4.8 Do Not Infer Pregnancy Safety From Traditional Use

Several studies in the source review involve miscarriage models or formulas used during pregnancy.

These findings do not justify recommending an untested Cuscuta–Cistanche supplement during pregnancy, while trying to conceive, or during fertility treatment.

Reproductive-health development should specifically consider:

Potential estrogen-like or other hormonal activity.

Interactions with fertility medications and other medicines.

Reproductive and developmental safety.

Differences between male and female target populations.

Appropriate exclusion criteria and professional oversight.

The Commercial Takeaway

For Cistanche factories and botanical supplement brands, the strongest opportunity is not to promise more than the evidence supports.

It is to offer a better-documented ingredient platform:

authenticated raw materials, transparent extraction, reproducible composition, clearly defined formulation ratios, relevant safety data, and research on the actual finished product.

That approach is more useful to serious buyers-and more defensible-than describing a traditional pairing as a clinically proven fertility solution.

 

References

All 55 references supplied with the source text are retained below. Article titles are translated into English for readability; translated titles are descriptive and may differ from publisher-supplied English titles. The original bibliography has not been independently verified.

Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Vol. I. Beijing: China Medical Science Press; 2020. [In Chinese.]

Gu Guanguang. Shen Nong Ben Cao Jing. Facsimile edition. Beijing: People's Medical Publishing House; 1955. [In Chinese.]

Huang Mingzhu, Wang Jinglong, Cui Xiaoping, et al. Research progress on the pharmacological activities of Cuscuta seed. Journal of Anhui University of Chinese Medicine. 2023;42(5):101–104. [In Chinese.]

Zan Shujie, Wang Kai, Li Lin, et al. An interpretation of the theory of herbal-pair compatibility. Journal of Traditional Chinese Medicine. 2023;64(17):1729–1733. [In Chinese.]

Xia Huifang, Wang Yu. Protective effects of an aqueous Cuscuta seed extract against cyclophosphamide-induced reproductive injury in male mice. Heilongjiang Animal Science and Veterinary Medicine. 2017;(11):200–203, 297. [In Chinese.]

Li Lijuan, Liu Wentao, Luo Huanhuan, et al. Effects of total Cuscuta flavonoids on the apoptosis-related proteins Bax, Bcl-2, and caspase-3 in mouse Leydig cells. Academic Journal of Chinese PLA Medical School. 2022;43(2):199–204. [In Chinese.]

Guo Shilei, Zhang Liyun, Li Zhiqiang, et al. Effects of Cuscuta flavonoids on spermatogenic function in rats with varicocele. Anatomy Research. 2022;44(5):419–424. [In Chinese.]

Tao Jinliang, Wang Xiao, Wei Yuanyuan, et al. Protective effects of Cuscuta flavonoids against BPA-induced abnormalities in androgen secretion by mouse Leydig cells. Progress in Veterinary Medicine. 2019;40(5):71–75. [In Chinese.]

Sun Xiangming, Song Hui, Zhao Lizhu, et al. Identification of constituents directly responsible for the estrogen-like effects of Cuscuta seed in vivo. Acta Pharmaceutica Sinica. 2021;56(7):1826–1831. [In Chinese.]

Zhang Yan, Li Yang, Gao Nana, et al. Effects of three Chinese medicinal polysaccharides on delaying ovarian functional decline in naturally aging mice. Chinese Journal of Veterinary Medicine. 2024;60(9):114–121. [In Chinese.]

Liu Ying, Zhao Qianhui, Chuai Yanan, et al. Cuscuta flavonoids alleviate reproductive injury in adult female offspring following bisphenol A exposure during pregnancy. Chinese Journal of Veterinary Science. 2024;44(3):536–542. [In Chinese.]

Xie Ying, Xiao Min, Jiang Xiaocui, et al. Mechanisms of Cuscuta seed in preventing and treating premature ovarian failure based on the lipid and atherosclerosis pathway. Chinese Journal of Experimental Traditional Medical Formulae. 2024;30(6):109–118. [In Chinese.]

Zhao Qianying, Wang Dongcai, Wu Haibin, et al. Effects and mechanisms of total Cuscuta flavonoids on serum thyroid hormones and ovulatory dysfunction in rats with PCOS. Guiding Journal of Traditional Chinese Medicine and Pharmacy. 2022;28(5):30–34, 46. [In Chinese.]

Meng Zhuoran, Zhao Ziming, Jia Zhuangzhuang, et al. Effects and mechanisms of orally administered Cuscuta seed ethanol extract on postmenopausal osteoporosis in rats. Shandong Medical Journal. 2024;64(17):29–32. [In Chinese.]

Zhang Tiandong, Peng Qingping, Liu Huan, et al. Cuscuta seed for osteoarthritis: Network pharmacology analysis and experimental validation. Chinese Journal of Tissue Engineering Research. 2024;28(28):4516–4521. [In Chinese.]

Liang Chen. Effects of an aqueous Cuscuta seed extract on bone healing in rats with osteoporotic fractures. Journal of Sichuan of Traditional Chinese Medicine. 2023;41(4):48–52. [In Chinese.]

Sun Qihua, Cai Honghui, He Aiyu, et al. Cuscuta flavonoids affect osteoblast apoptosis by regulating ZBED3-AS1. Chinese Journal of Pathophysiology. 2021;37(2):306–314. [In Chinese.]

Ye Chunlin, Khudoyberdiev Ilkhomjon, Chen Ying, et al. Antioxidant activity and inhibition of tumor-cell proliferation by Cuscuta polysaccharides. Journal of Henan University of Technology (Natural Science Edition). 2020;41(5):73–78. [In Chinese.]

Xiao Xiang, Wu Xuanyu. Screening key genes involved in the pancreatic inflammation–cancer transition and predicting Chinese medicinal interventions. Chinese Traditional and Herbal Drugs. 2022;53(15):4795–4806. [In Chinese.]

Song Hui, Huang Xiaoqiao, Sun Xiangming, et al. Mechanisms of the anti-breast-cancer activity of Cuscuta seed ethanol extract based on network pharmacology, molecular docking, and animal experiments. Chinese Traditional and Herbal Drugs. 2024;55(14):4747–4758. [In Chinese.]

Sun Yue, Bao Yongrui, Wang Shuai, et al. Compatibility patterns of pharmacologically active fractions from Compound Muji Granules in inducing HepG2 cell apoptosis using microfluidic chip technology. World Science and Technology-Modernization of Traditional Chinese Medicine and Materia Medica. 2021;23(10):3606–3612. [In Chinese.]

Zheng Yibo, Yang Xinxin, Bao Yongrui, et al. Mechanisms of the anti-liver-cancer activity of total Cuscuta flavonoids based on PI3K/PTEN/VEGF signaling. Chinese Journal of Hospital Pharmacy. 2018;38(14):1462–1465. [In Chinese.]

Qin Jingjing, Qian Huiqin, Wei Jing, et al. Extraction process and antioxidant activity of total flavonoids from Cuscuta seed. Science and Technology of Food Industry. 2019;40(23):151–157. [In Chinese.]

Liu Haiyun, Ji Yulong, He Zhijian. Effects of Cuscuta seed extract on learning and memory and ATPase activity in liver and brain tissues of naturally aging mice. Chinese Journal of Gerontology. 2018;38(23):5794–5796. [In Chinese.]

Wu Xiaoying, Zhang Xuelan, Mo Qiuyi, et al. Establishment of UPLC fingerprints of Cuscuta seed extracts and analysis of antioxidant spectrum–effect relationships. China Pharmacist. 2023;26(11):225–232. [In Chinese.]

Chen Xuemei, Yang Xiaoxin, Zhu Zhengyan, et al. Effects of total Cuscuta flavonoids applied at the Sanyinjiao acupoint on pregnancy outcomes and Th1/Th2 cytokine balance in rats with miscarriage. Journal of Practical Obstetrics and Gynecology. 2023;39(7):535–540. [In Chinese.]

Wang Zhigang, Qi Feng, Li Yinghong, et al. Mechanisms of Cuscuta seed in insulin resistance based on network pharmacology and molecular docking. Clinical Rational Drug Use. 2024;17(8):1–6, 15. [In Chinese.]

Zhang Dongqiang, Liu Zhixin. Separation and purification of Cuscuta polyphenols and their effects on exercise-related fatigue. China Food Additives. 2023;34(10):186–193. [In Chinese.]

Zhao Qian, Luo Hongbin, Ling Zhifeng, et al. Effects of Cuscuta seed on cognitive impairment in a rat model of Alzheimer's disease through GSK-3β signaling. Chinese Pharmacological Bulletin. 2021;37(12):1775–1776. [In Chinese.]

Lei Wei, Huang Caihong, Ren Hezhuang, et al. Effects of Cuscuta seed on intestinal inflammation, intestinal microbiota, and intestinal mucosal microstructure in young rats with chronic diarrhea. Practical Pharmacy and Clinical Remedies. 2021;24(10):871–875. [In Chinese.]

Zhao Cong, Wang Bin, Zhao Qi, et al. Effects of the Cuscuta seed–goji berry pairing on testicular tissue structure and sperm quality in a mouse model of oligoasthenozoospermia. Chinese Journal of Andrology. 2023;37(3):71–75. [In Chinese.]

Wang Jisheng, Bao Binghao, Deng Sheng, et al. Effects of Cuscuta seed–goji berry on proliferation and apoptosis in a spermatogonial dysfunction model induced by Tripterygium glycosides. China Medical Herald. 2022;19(31):5–9. [In Chinese.]

Bao Binghao, Deng Sheng, Feng Junlong, et al. Experimental study of the Cuscuta seed–goji berry pairing in improving spermatogonial dysfunction through PI3K/AKT pathway regulation. Chinese Journal of Andrology. 2022;36(6):31–35, 47. [In Chinese.]

Deng Sheng, Li Haisong, Wang Bin, et al. Effects of Cuscuta seed–goji berry on proliferation- and apoptosis-related proteins in rats with oligoasthenozoospermia through PI3K/AKT signaling. China Journal of Traditional Chinese Medicine and Pharmacy. 2023;38(2):795–799. [In Chinese.]

Zong Zheng, Hu Yang, Xu Beilei, et al. Constituents and mechanisms of the Cuscuta seed–goji berry pairing in premature ovarian insufficiency based on UPLC-Q-TOF-MS and network pharmacology. Chinese Traditional Patent Medicine. 2025;47(2):649–658. [In Chinese.]

Li Jinying, Zhang Zhaoping, Ye Jinfei, et al. Mechanisms of the Cuscuta seed–goji berry pairing in premature ovarian failure based on network pharmacology. China Pharmacy. 2020;31(18):2202–2209. [In Chinese.]

Guan Siqi, Zhu Yutian, Dong Lei, et al. Mechanisms by which the Cuscuta seed–goji berry pairing repairs the blood–testis barrier in rats with impaired spermatogenesis. The Chinese Journal of Human Sexuality. 2020;29(2):100–107. [In Chinese.]

Liu Min, Shi Wei, Yang Jing, et al. Effects of Xinjia Congrong Tusizi Decoction on granulosa-cell ferroptosis in rats with premature ovarian insufficiency through p53/Nrf2 signaling. Chinese Journal of Experimental Traditional Medical Formulae. 2024;30(7):104–111. [In Chinese.]

Shi Wei, Liu Min, Wang Zhichao, et al. Effects of Xinjia Congrong Tusizi Decoction-containing serum on mitochondrial energy metabolism, oxidative stress, and dynamics in human ovarian granulosa cells exposed to triptolide. Journal of Chinese Medicinal Materials. 2023;46(10):2573–2578. [In Chinese.]

Shi Wei, Liu Min, Wang Zhichao, et al. Xinjia Congrong Tusizi Decoction promotes mitochondrial biogenesis through SIRT1/PGC-1α signaling to repair ovarian granulosa-cell injury. World Science and Technology-Modernization of Traditional Chinese Medicine and Materia Medica. 2024;26(5):1269–1278. [In Chinese.]

Shi Wei, Yin Xuemei, Wang Zhichao, et al. Effects of Xinjia Congrong Tusizi Decoction on mitochondrial function in rats with diminished ovarian reserve through AMPK/SIRT1 signaling. Chinese Traditional Patent Medicine. 2023;45(10):3221–3227. [In Chinese.]

Liu Xiaohong, Huo Junyi, Luo Qian, et al. Selected clinical experience of Professor Wu Keming in using Xinjia Congrong Tusizi Pills for premature ovarian failure with successful pregnancy outcomes. Yunnan Journal of Traditional Chinese Medicine and Materia Medica. 2016;37(4):19–22. [In Chinese.]

Liu Xianhui, Guo Xiaona, Lu Jinjin, et al. Modified Da Tusizi Decoction for aplastic anemia complicated by femoral head necrosis: Seven cases. Traditional Chinese Medicinal Research. 2011;24(12):44–45. [In Chinese.]

Li Qian, Wang Yonghong. A data-mining analysis of prescribing patterns among renowned gynecological practitioners treating PCOS. Guangming Journal of Chinese Medicine. 2024;39(9):1706–1709. [In Chinese.]

Wang Cuicui, Ma Xiaoxin. Targets and signaling pathways of dong quai–Cuscuta seed in polycystic ovary syndrome based on network pharmacology. Journal of China Medical University. 2021;50(1):51–56. [In Chinese.]

Yuan Renzhi, Tang Peng, Xiao Weiqiong, et al. Network pharmacology mechanisms of dong quai–Cuscuta seed in polycystic ovary syndrome with a Kidney-deficiency and blood-stasis pattern. Journal of New Chinese Medicine. 2020;52(3):83–88. [In Chinese.]

Jian Huanling, Zhao Ying. Clinical study of Zishen Yutai Pills combined with Zigui Yijing Decoction for premature ovarian insufficiency. Journal of Guangzhou University of Traditional Chinese Medicine. 2021;38(4):703–711. [In Chinese.]

Fan Lipeng, Sun Zixue, Men Bo, et al. Clinical study of Yishen Tongluo Formula in improving sperm mitochondrial membrane potential. Journal of Chinese Medicinal Materials. 2024;47(6):1553–1556. [In Chinese.]

Sun Zixue, Chen Yangdi, Chen Jianshe, et al. Clinical observation of Yishen Tongluo Formula for infertility associated with oligoasthenozoospermia and a Kidney-deficiency and collateral-obstruction pattern. Chinese Archives of Traditional Chinese Medicine. 2024;42(8):1–6. [In Chinese.]

Xu Jin, Zhang Wenting, Wang Shiguang. Network pharmacology mechanisms of the Achyranthes root–Cuscuta seed pairing in preventing and treating hypertensive kidney injury. Clinical Journal of Traditional Chinese Medicine. 2024;36(2):289–295. [In Chinese.]

Qu Wei. Effective prescriptions and clinical experience of Qu Wei: Shenshuai Mixture. Jiangsu Journal of Traditional Chinese Medicine. 2022;54(12):11–12. [In Chinese.]

Li Hemei, Shi Minyan, Feng Chaoxiong. Association-rule mining of prescribing patterns in Chinese herbal formulas for recurrent spontaneous abortion. Acta Chinese Medicine and Pharmacology. 2015;43(6):42–45. [In Chinese.]

Liu Yuanyuan. Effects of modified Shoutai Wan on serum β-hCG and inflammatory factors in patients with early threatened miscarriage and a Kidney-deficiency pattern. Drug Evaluation. 2023;20(2):229–231. [In Chinese.]

Han Han, Zhang Yuehui, Han Yapeng, et al. Mechanisms of modified Shoutai Wan in patients with PCOS and early threatened miscarriage from the perspective of ferroptosis. Acta Chinese Medicine and Pharmacology. 2023;51(10):67–71. [In Chinese.]

Fan Cailian, Xu Chuanhua. Molecular mechanisms of the Atractylodes macrocephala–Cuscuta seed pairing in polycystic ovary syndrome based on network pharmacology. Medical Information. 2024;37(2):47–54. [In Chinese.]