Rehmannia Root extract (Rehmannia root extract) is mainly used in traditional medicine to nourish Yin and blood, and the active ingredient Catalpol content is 1.2%-3.5% (HPLC detection), which can stimulate bone marrow hematopoietic function. A clinical study (NCT03871605) showed that supplementation of a compound formula with 300mg of Rehmannia Root extract once daily increased hemoglobin by 18.7% and red blood cell count by 12.3% in anemic patients after 8 weeks. In the “Chinese Pharmacopoeia”, the processing standard of raw Rehmannia is extract ≥65%, and the polysaccharide content in cooked Rehmannia after steaming and drying for nine times is increased to 35%-40%, and the Yin nourishing effect is increased 2.3 times.
In anti-inflammatory application, Verbascoside of Rehmannia Root extract was IC50 4.8μM for COX-2, 62% lower than ibuprofen. In the rheumatoid arthritis model, intragastric administration of 200mg/kg of the extract reduced joint swelling volume by 54% and IL-6 by 67%. A traditional Chinese medicine hospital combined it with Astragalus extract (ratio 6:4) into a paste, patients’ pain VAS score improved from 7.2 to 3.1 points, effective rate was 89%.
Rehmannia Root extract in the treatment of diabetes increases insulin resistance by activating AMPK pathway. In animal experiments, dosage of 100mg/kg was shown to reduce fasting blood glucose by 31% and islet β cell apoptosis by 43%. Phase III clinical trial of a proprietary Chinese medicine in the market (15% extract of Rehmannia Root) indicated that patients’ HbA1c, following 12 weeks of treatment with metformin, was enhanced from 8.6% to 6.9%, which was better than that of the Western medicine alone group (down to 7.5%).
The anti-aging mechanism is by regulating the telomerase activity. In vitro assays showed that 50μg/mL Rehmannia Root extract extended the human fibroblast telomere length by 19% and decreased the age-related β-galactosidase positive rate by 42%. The skin elasticity of the volunteers was enhanced by 27% (Cutometer MPA580) and wrinkle density decreased by 33% following 12 weeks of use of a brand of anti-wrinkle serum (containing 2% extract).
The liver protection was quantitatively verified. Rehmannia Root extract (400mg/kg) reduced serum ALT level from 586 U/L to 189 U/L (68% reduction) in CCL4-induced liver damage model mice, and restored GSH content to 82% of normal level. A drug company combined it with schisandra extract, and in 3 months of therapeutic trial for patients with alcoholic liver disease, the liver stiffness value (FibroScan) was decreased from 9.8 kPa to 6.3 kPa, which was better than 7.9 kPa in the control group.
In gynecological application, Rehmannia Root extract regulates estrogen receptor ERα/ERβ balance. In 8 weeks, the frequency of hot flashes decreased from 5.2 to 2.1 times daily in menopausal women who received 500mg of extract daily, and bone mineral density T-value increased by 0.12 (control group decreased by 0.05). A classical prescription “Liuwei Rehmannia pill” that contains 23% cooked rehmannia has been shown to increase the level of AMH in premature ovarian failure patients from 0.38 ng/mL to 1.12 ng/mL.
The neuroprotective actions were clear. Rehmannia Root Extract (0.5% concentration) inhibited Aβ42 fiber formation by 73% and Alzheimer’s disease model mice cognitive function (Morris water maze escape latency was decreased by 58%). In a clinical trial of a cognitive function supplement containing 200mg of the extract, the subject’s MMSE score was increased by 3.7 points (compared with 0.8 points for the placebo group).
Novel formulation technology enhances bioavailability. Nano-encapsulated Rehmannia Root extract (particle size ≤100nm) Cmax and AUC0-24h were 4.2 times that of traditional aqueous decoction in intestinal absorption test. Supercritical CO2 extraction technology was used in a pharmaceutical company to increase catalpol extraction rate from 1.8% to 4.1%, and the production cost was reduced by 37%.
Safety tests revealed that LD50 (rat oral) of Rehmannia Root extract was > 5000mg/kg, and teratogen tests were negative. However, long-term dosing (> 1000mg/day) can prolong the metabolic half-life of warfarin (from 36 hours to 52 hours), which requires monitoring INR values. Rehmannia extract market will reach 270 million US dollars worldwide in 2023, wherein anti-aging and metabolic diseases will hold more than 60%, with the CAGR of 8.9% expected in 2025.