Rehmannia

In traditional Chinese medicine, cured (prepared) and uncured (fresh) rehmannia are used differently. Uncured rehmannia is used to reduce fevers and “heat” conditions, as a haemostatic 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, by contrast, 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 often associated with longevity. It is regarded as a yin jing tonic and is frequently added to formulas intended to strengthen sexual function — a traditional-use attribution rather than a pharmacologically demonstrated effect ^{39Reference 39Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

This is the deepest part of the file. Catalpol lowers blood glucose across many rodent models — for example in streptozotocin-induced diabetic rats, where oral catalpol improved glucose handling and insulin sensitivity ^{2Reference 2Huang WJ et al. · 2010AnimalAntihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats — animal modelView study →}, with the anti-diabetic effect replicated at 2.5–200 mg/kg across rat and mouse studies and mapped to AMPK/PI3K-Akt, PPAR and AGE/RAGE signalling in two detailed reviews ^{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 independently active: oral administration reduced hyperglycemia, hyperlipidemia and vascular inflammation in STZ-diabetic mice ^{3Reference 3Zhou J et al. · 2015AnimalRehmannia glutinosa polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice — animal modelView study →}. On the human side, evidence exists only for multi-herb formulas — a 48-week Rehmannia-6-based formula slowed eGFR decline 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 →}, and a Liuwei Dihuang (six-ingredient Rehmannia pill) plus metformin retrospective study reported better glycemic and inflammatory indices 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 randomised 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.

A coherent body of animal work supports liver protection. Hepatoprotective iridoid glycosides were isolated directly from the roots and shown to reduce hepatocyte 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 →}, and a prepared-root aqueous extract protected against hepatic ischemia/reperfusion injury by restoring iron homeostasis 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 blunted 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 →}.

Gap: entirely rodent and cell-based; no human liver-endpoint data, and the effective doses and extract types differ across studies, so no consistent preparation can be recommended.

Anti-inflammatory activity is broad but mostly attributable to the polysaccharide and to iridoids rather than the whole crude root. A purified arabinan suppressed ROS and downregulated 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 comprehensive 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 →}.

Gap: the active fraction (polysaccharide vs iridoid) and dose are not standardised, and there is no human anti-inflammatory endpoint; much of the whole-herb activity is inferred from isolated fractions.

Catalpol is one of the more compelling natural neuroprotectants in preclinical work. In a β-amyloid-plus-glutamate memory-defect model, catalpol was comparable to donepezil at reducing Alzheimer markers through a non-cholinergic mechanism ^{15Reference 15Xia Z et al. · 2012AnimalMemory defect from β-amyloid plus glutamate agonist alleviated by catalpol and donepezil through different mechanisms — animal modelView study →}; rehmannioside A improved post-ischemic cognitive impairment and limited ferroptosis via PI3K/AKT/Nrf2 and SLC7A11/GPX4 signalling in rats ^{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 →}; and catalpol protected the neurovascular unit in ischemic-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 →}.

Gap: exclusively animal and in vitro; no clinical neurological endpoints, and most effects use isolated catalpol or rehmannioside A, often by injection, not oral whole root.

Rehmannia is traditionally a kidney herb, and preclinical work is consistent with renal protection. Oleic acid isolated from the root alleviated LPS-induced acute kidney injury via Ras/MAPK/PPAR-γ signalling in mice ^{13Reference 13Zhang B et al. · 2022AnimalOleic acid (from Rehmannia glutinosa) alleviates LPS-induced acute kidney injury via Ras/MAPK/PPAR-γ — animal modelView study →}, and the crude root inhibited renal fibrosis through a miR-122-5p/PKM axis in a rodent model ^{14Reference 14Liu X et al. · 2022AnimalRadix Rehmannia glutinosa inhibits renal fibrosis via miR-122-5p/PKM axis — animal modelView study →}. The strongest human signal is indirect: the Rehmannia-6-based formula RCT slowed eGFR decline and reduced albuminuria in diabetic chronic kidney disease over 48 weeks ^{5Reference 5Chan KW et al. · 2023RCTAdd-on Rehmannia-6-based Chinese medicine in type-2 diabetes and CKD — multicenter randomised controlled trialView study →}.

Gap: the one supportive human trial tests a formula, not the root; monotherapy renal endpoints are untested, and the crude-root fibrosis data are single-model.

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 →}, and a hot-compressed-steamed polysaccharide 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 →}. An older study also reported inhibition of immediate-type (IgE-mediated) allergic reactions by the root ^{26Reference 26Kim H et al. · 1998AnimalEffect of Rehmannia glutinosa on immediate-type allergic reaction — animal modelView study →}, consistent with the herb’s traditional antiallergic use.

Gap: the human data are limited to isolated cells in culture; whole-animal and human immune-outcome data for defined preparations are lacking.

A consistent set of rodent studies supports an antidepressant-like effect for catalpol. It ameliorated depressive-like behaviour in chronic-unpredictable-mild-stress 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 →}, and 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 →}, with a later study reporting sex-differences (stronger response in females) mediated by SIRT1-linked synaptic plasticity ^{22Reference 22Wu X et al. · 2024AnimalSIRT1-mediated synaptic plasticity and sex-differences in antidepressant efficacy of catalpol — animal modelView study →}. Separately, a Lily-bulb/fresh-Rehmannia co-decoction and its key phenylethanoid verbascoside reduced chronic-stress depression 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 →}.

Gap: no human antidepressant trials of Rehmannia or catalpol as a defined agent; the co-decoction result is confounded by a second herb.

Preclinical work links Rehmannia to bone preservation, mostly via the polysaccharide. It alleviated diabetic osteoporosis and peripheral neuropathic 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 →}, and reduced bone loss and skeletal-muscle atrophy in a disuse/ovariectomy rat model ^{28Reference 28Ou L et al. · 2021AnimalEffects of Rehmannia glutinosa polysaccharides on bone structure and skeletal-muscle atrophy in disuse rats — animal modelView study →}. A Rehmannia-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 →}.

Gap: all rodent; no human bone-density or fracture data, and the herb-pair study cannot isolate Rehmannia’s contribution.

This aligns with the traditional “blood-building” use of prepared Rehmannia. The root polysaccharide reversed busulfan-induced marrow failure in aplastic-anemia 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 →}, and the steamed polysaccharide relieved cyclophosphamide-induced haematopoietic insufficiency alongside its immune effects ^{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 →}.

Gap: confined to mouse marrow-failure models; no human haematological endpoints, and activity is specific to the polysaccharide fraction, not the whole root at dietary intake.

Antioxidant activity is real but mostly demonstrated at the constituent and chemical-assay level rather than as a whole-herb clinical effect. Acetylated derivatives of the root polysaccharide showed enhanced 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 ischemia ^{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 →}. In practice antioxidant capacity underpins the hepato-, neuro- and nephroprotective findings rather than standing as an independent indication.

Gap: dominated by in-vitro assays and chemically modified fractions; no human oxidative-stress biomarker data for a standard preparation.

This is the herb’s signature Western claim (“adrenal tonic”), but the mechanistic evidence is thin. The main direct study reports that catalpol reduced elevated cortisol and lowered CRH and ACTH — modulating the hypothalamic-pituitary-adrenal axis — in an Alzheimer’s-disease rat model ^{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 adaptogen-like stress 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.

Rehmannia is regarded as a low-toxicity herb with a long food-and-medicine history, and no serious adverse effects are reported in the pharmacological literature for normal medicinal use ^{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 →}. The most concrete interaction signal is metabolic: the marker iridoid catalpol inhibits human liver cytochrome-P450 enzymes CYP3A4, CYP2E1 and CYP2C9 in vitro, so caution is reasonable when Rehmannia-containing products are combined with drugs cleared by those enzymes, though this has not been confirmed in humans ^{33Reference 33Liu L et al. · 2019In vitroEffects of catalpol on the activity of human liver cytochrome P450 enzymes — in vitroView study →}. In traditional practice the fresh/uncured root is considered cooling and can loosen the stool, so it is used cautiously in people with poor digestion or diarrhoea; the classical caution about combining Rehmannia with corticosteroids is based on presumed HPA-axis activity and is not established by controlled human data ^{32Reference 32Wang JH et al. · 2014AnimalCatalpol regulates function of the hypothalamic-pituitary-adrenocortical axis in an Alzheimer’s-disease rat model — animal modelView study →}.