Rehmannia

In traditional Chinese medicine, cured (prepared) and uncured rehmannia are used differently. Uncured rehmannia is used to reduce fevers and “heat” conditions, as a hemostatic to remove heat from the blood, and for rashes, low-grade fevers, diabetes and bleeding ^{38Reference 38Bone K · 2013Principles and Practice of Phytotherapy (2nd ed.)}.

Cured rehmannia is used to regulate menstruation, promote blood production, and correct anaemia, dizziness, weakness, tinnitus, amenorrhoea and metrorrhagia ^{38Reference 38Bone K · 2013Principles and Practice of Phytotherapy (2nd ed.)}.

Fresh Rehmannia

Added to formulas to tonify yin in the liver, kidney and heart, contributing cooling, anti-inflammatory actions ^{38,39Reference 38Bone K · 2013Principles and Practice of Phytotherapy (2nd ed.)Reference 39Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

Prepared Rehmannia

Prepared rehmannia is a fundamental kidney tonic in Chinese herbalism and is associated with longevity. It is regarded as a yin jing tonic and is frequently added to formulas intended to strengthen sexual function ^{39Reference 39Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

Catalpol purified from the root lowered plasma glucose when injected into streptozotocin-diabetic rats. It also increased glucose uptake into muscle and glycogen synthesis in liver cells ^{2Reference 2Huang WJ et al. · 2010AnimalAntihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats — animal modelView study →}.

Across rat and mouse studies, catalpol has been given by mouth at 2.5–200 mg/kg, and two reviews map its effects to AMPK/PI3K-Akt, PPAR and AGE/RAGE signalling ^{1,4Reference 1Bhattamisra SK et al. · 2021ReviewMolecular and biochemical pathways of catalpol in alleviating diabetes mellitus and its complications — reviewView study →Reference 4Bai Y et al. · 2019ReviewCatalpol in diabetes and its complications: pharmacology, pharmacokinetics and safety — reviewView study →}.

The root polysaccharide fraction is active on its own: given by mouth, it reduced high blood sugar, high blood lipids and vascular inflammation in streptozotocin-diabetic mice ^{3Reference 3Zhou J et al. · 2015AnimalRehmannia glutinosa polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice — animal modelView study →}.

In people, evidence exists only for multi-herb formulas. A 48-week Rehmannia-6-based formula slowed the decline in kidney function in type 2 diabetes with kidney disease ^{5Reference 5Chan KW et al. · 2023RCTAdd-on Rehmannia-6-based Chinese medicine in type-2 diabetes and CKD — multicenter randomised controlled trialView study →}. In a retrospective study of 80 older patients, Liuwei Dihuang pill (six-ingredient Rehmannia pill) plus metformin gave lower fasting and post-meal glucose than metformin alone ^{6Reference 6Li N et al. · 2023Clinical trialLiuwei Dihuang (six-drug Rehmannia bolus) as adjunct to metformin in senile type-2 diabetes — clinical studyView study →}.

Gap: no randomized trial has tested Rehmannia root, catalpol, or the polysaccharide as a single agent for glycemic control in humans; all human data are confounded by co-formulated herbs.

Iridoid glycosides isolated from the roots moderately reduced liver-cell injury in vitro ^{7Reference 7Liu YF et al. · 2012In vitroHepatoprotective iridoid glycosides from the roots of Rehmannia glutinosa — in vitroView study →}.

Catalpol reduced liver fibrosis in mice by inhibiting hepatic-stellate-cell aerobic glycolysis via EphA2/FAK/Src signalling ^{8Reference 8Zhang Q et al. · 2024In vitroCatalpol ameliorates liver fibrosis via inhibiting aerobic glycolysis (EphA2/FAK/Src) — mouse model, in vitroView study →}. A prepared-root water extract protected against hepatic ischaemia/reperfusion injury in mice by restoring iron balance and limiting ferroptosis ^{9Reference 9Zhang Y et al. · 2024AnimalRehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring iron homeostasis — animal modelView study →}.

The root polysaccharide also reduced LPS-induced acute liver injury in mice ^{10Reference 10Qiao H et al. · 2025AnimalAnti-inflammatory effects of Rehmannia glutinosa polysaccharide on LPS-induced acute liver injury — mouse modelView study →}.

All of this work is in rodents and cells, with no human liver data and no consistent preparation across studies.

Anti-inflammatory activity comes mostly from the polysaccharides and the iridoids rather than from studies of the whole root. A purified arabinan suppressed ROS and lowered TNF-α, IL-1β and IL-6 in vivo and in vitro ^{11Reference 11Zhang H et al. · 2023In vitroStructural characterization and anti-inflammatory effects of an arabinan from Rehmannia glutinosa — in vivo, in vitroView study →}, and the polysaccharide reduced inflammatory signalling in LPS-induced acute liver injury ^{10Reference 10Qiao H et al. · 2025AnimalAnti-inflammatory effects of Rehmannia glutinosa polysaccharide on LPS-induced acute liver injury — mouse modelView study →}.

A review of iridoid glycosides places catalpol and aucubin among iridoids that lower COX-2 and inflammatory cytokines ^{12Reference 12Chaitanya MVNL et al. · 2025ReviewDeciphering the iridoids’ boundaries: adaptogenic and anti-inflammatory properties — reviewView study →}.

The active fraction and dose are not standardised, and there is no human endpoint.

In mice given β-amyloid plus a glutamate-receptor agonist, both catalpol and donepezil improved learning and memory over two to three months, by different mechanisms. Catalpol fully restored muscarinic receptor density and choline acetyltransferase activity and raised brain BDNF, which donepezil did not ^{15Reference 15Xia Z et al. · 2012AnimalMemory defect from β-amyloid plus glutamate agonist alleviated by catalpol and donepezil through different mechanisms — animal modelView study →}.

Injected rehmannioside A improved cognitive impairment after ischaemia in rats and limited ferroptosis via PI3K/AKT/Nrf2 and SLC7A11/GPX4 signalling ^{16Reference 16Fu C et al. · 2022In vitroRehmannioside A improves cognitive impairment and alleviates ferroptosis (PI3K/AKT/Nrf2, SLC7A11/GPX4) after ischemia — rat model, in vitroView study →}.

Intravenous catalpol reduced infarct volume and protected the neurovascular unit in ischaemic-stroke rats through VEGF-PI3K/AKT and VEGF-ERK signalling ^{17Reference 17Wang HJ et al. · 2022AnimalCatalpol improves the neurovascular unit in ischemic-stroke rats via VEGF-PI3K/AKT and VEGF-ERK signalling — animal modelView study →}.

Two reviews summarise catalpol’s activity across Alzheimer’s and Parkinson’s models ^{18,19Reference 18Zhang X et al. · 2021ReviewTherapeutic potential of catalpol and geniposide in Alzheimer’s and Parkinson’s diseases — reviewView study →Reference 19Dinda B et al. · 2019ReviewTherapeutic potentials of plant iridoids in Alzheimer’s and Parkinson’s diseases — reviewView study →}.

This work is in animals and cells, and most of it uses isolated catalpol or rehmannioside A, often by injection rather than oral whole root.

Oleic acid isolated from the root reduced LPS-induced acute kidney injury in mice via Ras/MAPK/PPAR-γ signalling ^{13Reference 13Zhang B et al. · 2022AnimalOleic acid (from Rehmannia glutinosa) alleviates LPS-induced acute kidney injury via Ras/MAPK/PPAR-γ — animal modelView study →}. A prepared-root extract inhibited kidney fibrosis in mice after ureteral obstruction, through a miR-122-5p/PKM axis ^{14Reference 14Liu X et al. · 2022AnimalRadix Rehmannia glutinosa inhibits renal fibrosis via miR-122-5p/PKM axis — animal modelView study →}.

In people, a 48-week trial in 148 patients with type 2 diabetes and kidney disease added a Rehmannia-6-based formula to standard care. Kidney function (eGFR) declined 2.7 mL/min per year less than with standard care alone. The change in albuminuria was not significant ^{5Reference 5Chan KW et al. · 2023RCTAdd-on Rehmannia-6-based Chinese medicine in type-2 diabetes and CKD — multicenter randomised controlled trialView study →}.

The one supportive human trial tests a formula, not the root, and it was assessor-blinded without a placebo.

The root polysaccharide is the main immune-active fraction. It promoted maturation and activation of human dendritic cells in vitro ^{24Reference 24Wang Y et al. · 2018In vitroRehmannia glutinosa polysaccharide promotes activation of human dendritic cells — in vitroView study →}. A polysaccharide from hot-compressed steamed root activated TLR4/NF-κB signalling and reversed cyclophosphamide-induced immunosuppression and gut-microbiota disruption in mice ^{25Reference 25Jia Y et al. · 2024In vitroPolysaccharide from hot-compressed steamed Rehmannia glutinosa on the immune system and gut microbiota in immunosuppressed mice — animal model, in vitroView study →}.

A water extract of steamed root inhibited immediate-type (IgE-mediated) allergic reactions in rats and histamine release from mast cells ^{26Reference 26Kim H et al. · 1998AnimalEffect of Rehmannia glutinosa on immediate-type allergic reaction — animal modelView study →}.

Human data are limited to isolated cells in culture.

Catalpol reduced depressive-like behaviour in chronically stressed mice by suppressing oxidative-stress-driven NLRP3 inflammasome activation and neuroinflammation ^{20Reference 20Wang YL et al. · 2021AnimalCatalpol ameliorates depressive-like behaviour in CUMS mice via oxidative-stress-mediated NLRP3 inflammasome and neuroinflammation — animal modelView study →}. In chronically stressed rats it acted through heme-oxygenase-1-linked antioxidant and neurotrophic pathways ^{21Reference 21Wu X et al. · 2022AnimalCatalpol exerts antidepressant-like effects via HO-1 activation — animal modelView study →}. A later mouse study found a stronger response in females, linked to SIRT1-mediated synaptic plasticity ^{22Reference 22Wu X et al. · 2024AnimalSIRT1-mediated synaptic plasticity and sex-differences in antidepressant efficacy of catalpol — animal modelView study →}.

A co-decoction of lily bulb and fresh rehmannia, and its key phenylethanoid verbascoside, reduced chronic-stress depression in animals via the gut-microbiota-brain axis ^{23Reference 23Mao Q et al. · 2024AnimalLilii bulbus–Radix Rehmannia co-decoction and verbascoside inhibit neuroinflammation via the gut-microbiota-brain axis — animal modelView study →}.

There are no human antidepressant trials of rehmannia or catalpol, and the co-decoction result includes a second herb.

The root polysaccharide reduced diabetic osteoporosis and nerve pain in streptozotocin-diabetic mice by expanding regulatory T cells ^{27Reference 27Yue W et al. · 2024AnimalRehmannia glutinosa polysaccharide alleviates diabetic osteoporosis and peripheral neuropathic pain via regulatory T cells — mouse modelView study →}. It also reduced bone loss and skeletal-muscle wasting in rats with ovaries removed and hind limbs immobilised ^{28Reference 28Ou L et al. · 2021AnimalEffects of Rehmannia glutinosa polysaccharides on bone structure and skeletal-muscle atrophy in disuse rats — animal modelView study →}.

A prepared rehmannia and cornus herb pair prevented diabetic osteoporosis via PI3K/AKT signalling in diabetic rats ^{29Reference 29Hu SJ et al. · 2025AnimalShudihuang-Shanzhuyu (Rehmannia-Cornus) herb pair prevents diabetic osteoporosis via PI3K/AKT — animal modelView study →}.

All of it is in rodents, with no human bone-density or fracture data, and the herb-pair study cannot isolate rehmannia’s contribution.

Prepared rehmannia is traditionally used to build the blood. The root polysaccharide reversed busulfan-induced marrow failure in aplastic-anaemia mice by remodelling the bone-marrow microenvironment through HIF-1α/NF-κB signalling ^{31Reference 31Liu NA et al. · 2023AnimalRehmannia glutinosa polysaccharide regulates the bone-marrow microenvironment via HIF-1α/NF-κB in aplastic-anemia mice — animal modelView study →}. The steamed-root polysaccharide also relieved cyclophosphamide-induced hematopoietic insufficiency ^{25Reference 25Jia Y et al. · 2024In vitroPolysaccharide from hot-compressed steamed Rehmannia glutinosa on the immune system and gut microbiota in immunosuppressed mice — animal model, in vitroView study →}.

This is confined to mouse marrow-failure models, with no human blood-count endpoints.

Antioxidant activity has been shown mostly in chemical assays and for isolated constituents. Acetylated derivatives of the root polysaccharide showed stronger radical-scavenging activity in vitro ^{30Reference 30Li J et al. · 2022In vitroAcetylation of Rehmannia glutinosa polysaccharides and antioxidant activity of derivatives — in vitroView study →}, and rehmannioside A reduced oxidative damage and ferroptosis after cerebral ischaemia ^{16Reference 16Fu C et al. · 2022In vitroRehmannioside A improves cognitive impairment and alleviates ferroptosis (PI3K/AKT/Nrf2, SLC7A11/GPX4) after ischemia — rat model, in vitroView study →}.

There is no human biomarker data for a standard preparation.

“Adrenal tonic” is the herb’s signature Western claim. The main direct study used rats given β-amyloid as an Alzheimer’s model. The model raised cortisol and lowered ACTH and CRH, and catalpol at 5–10 mg/kg brought these hormone levels back toward normal, most clearly at 21 days ^{32Reference 32Wang JH et al. · 2014AnimalCatalpol regulates function of the hypothalamic-pituitary-adrenocortical axis in an Alzheimer’s-disease rat model — animal modelView study →}.

Broader reviews of iridoids describe stress-related and corticosterone effects for this compound class ^{12Reference 12Chaitanya MVNL et al. · 2025ReviewDeciphering the iridoids’ boundaries: adaptogenic and anti-inflammatory properties — reviewView study →}.

Gap: rests essentially on one disease-model rat study; the “prevents corticosteroid suppression of the HPA axis” claim widely repeated for Rehmannia has no controlled human confirmation.

Toxicity. No serious adverse effects are reported in the pharmacological literature for normal medicinal use, and catalpol is well tolerated in animal studies ^{4,33Reference 4Bai Y et al. · 2019ReviewCatalpol in diabetes and its complications: pharmacology, pharmacokinetics and safety — reviewView study →Reference 33Liu L et al. · 2019In vitroEffects of catalpol on the activity of human liver cytochrome P450 enzymes — in vitroView study →}.

Drug metabolism. In human liver microsomes, catalpol inhibited CYP3A4, CYP2E1 and CYP2C9, and left five other CYP enzymes unaffected ^{33Reference 33Liu L et al. · 2019In vitroEffects of catalpol on the activity of human liver cytochrome P450 enzymes — in vitroView study →}. Take care when rehmannia products are combined with drugs cleared by those enzymes. The effect has not been confirmed in people.

Digestion. In traditional practice the uncured root is considered cooling and can loosen the stool, so it is used cautiously in people with poor digestion or diarrhoea.

Corticosteroids. A classical caution applies to combining rehmannia with corticosteroids, based on presumed HPA-axis activity. It has not been tested in controlled human studies ^{32Reference 32Wang JH et al. · 2014AnimalCatalpol regulates function of the hypothalamic-pituitary-adrenocortical axis in an Alzheimer’s-disease rat model — animal modelView study →}.