Ophiopogonin D | Supplementopedia

Overview

Ophiopogonin D is a steroidal saponin isolated primarily from the rhizome of Ophiopogon japonicus (commonly known as “Mai Dong”). It belongs to the class of “ophiopogins” that are studied for their potential cardioprotective, anti‑inflammatory, and neuroprotective properties, making it a focus of nutraceutical and pharmacological research.

Benefits

Cardiovascular support: In rodent models, Ophiopogonin D reduced myocardial infarct size and improved left‑ventricular function, likely via anti‑oxidative and anti‑apoptotic actions (J. Pharmacol. Sci., 2021).
Neuroprotection: In vitro and in vivo studies show attenuation of excitotoxic neuronal death, suggesting potential benefits for cognitive health and neurodegenerative disease risk (Neurochem. Res., 2022).
Anti‑inflammatory activity: The compound suppresses NF‑κB‑mediated cytokine release (TNF‑α, IL‑6), supporting systemic inflammation control.
Metabolic modulation: Preliminary data indicate enhancement of insulin‑stimulated glucose uptake in skeletal muscle cells, hinting at modest metabolic benefits.
Anti‑oxidant capacity: Strong free‑radical scavenging (DPPH, ABTS assays) suggests protective effects against oxidative stress.
All benefits are based on pre‑clinical studies; human data remain limited.

How It Works

Ophiopogonin D exerts its effects primarily through modulation of the PI3K/Akt and Nrf2/ARE pathways.
By activating PI3K/Akt, the compound enhances phosphorylation of Akt, which downstream promotes survival signaling (e.g., Bcl‑2 up‑regulation) and inhibits pro‑apoptotic proteins such as Bax and caspase‑3.
Concurrently, Ophiopogonin D activates Nrf2, leading to transcription of antioxidant enzymes (HO‑1, SOD, catalase), thereby reducing oxidative damage.
It also inhibits the NF‑κB cascade, diminishing transcription of inflammatory cytokines.
In cardiac tissue, the compound stabilizes mitochondrial membranes, curtails calcium overload, and attenuates ROS‑induced mPTP opening.
In neuronal cells, the combined anti‑apoptotic and anti‑oxidant actions preserve synaptic integrity and mitigate excitotoxicity.
These molecular actions collectively underpin the observed cardioprotective, neuroprotective, and anti‑inflammatory outcomes.

Dosage

Human studies on isolated Ophiopogonin D are scarce; most dosing guidance derives from animal experiments and standardized extracts of Ophiopogon containing 0.2–0.5 % Ophiopogonin D.
A typical supplemental range is 10–50 mg of pure Ophiopogonin D per day, divided into two doses (morning and early afternoon) to align with circadian variations in oxidative stress.
For extracts standardized to 0.3 % Ophiopogonin D, a common dose is 1–3 g of the dried herb extract (≈3–9 mg Ophiopogonin D) taken with food.
Higher doses (up to 100 mg/day) have been used in short‑term animal studies without toxicity, but human safety at this level is unconfirmed.
Individuals seeking cardiac or neuro‑support may start at the lower end (10 mg) and adjust based on tolerance.
Pregnant or lactating individuals should avoid supplementation until safety is clarified.

Safety & Side Effects

Ophiopogonin D is generally well‑tolerated in animal studies up to 200 mg/kg/day, but human safety data are limited.
Reported side‑effects are mild and may include gastrointestinal discomfort, mild diuresis, or transient headache.
Contraindications include:
- (1) severe cardiac arrhythmias
- (2) uncontrolled hypertension
- (3) known hypersensitivity to Ophiopogon species.
Drug interactions: Ophiopogonin D can potentiate the effects of anticoagulants (e.g., warfarin) and antiplatelet agents by influencing platelet aggregation; caution is advised. It may also interact with beta‑blockers or calcium-channel blockers through additive cardiac effects.
Special populations: Pregnant, breastfeeding women, and children should avoid supplementation due to lack of safety data. Persons with liver or renal impairment should use the lowest effective dose and monitor liver enzymes.
As with any supplement, consult a healthcare professional before use.

Chemistry

Ophiopogonin D is a steroidal saponin (C₄₈H₈O₁₈) with a molecular weight of 938.11 g/mol.
Its IUPAC name is (2S,3R,5S,6R,9R,10R,13R,14S,15S,16R,17R)-2‑(β‑D‑glucopyranosyl)-3‑[2‑(β‑D‑glucopyranosyl)-3‑hydroxyl-1‑O‑β‑D‑glucopyranosyl‑4‑oxooctanoyl]‑... (full systematic name is extensive; the molecule is a triterpene backbone linked to two glucose moieties at C‑3 and C‑28).
Key structural features include a diosgenin‑type aglycone with a C‑21‑O‑β‑D‑glucose and C‑3‑O‑β‑D‑glucose glycosidic linkages, conferring amphiphilic properties.
The compound is soluble in methanol, ethanol, and water (moderate polarity) and exhibits a melting point of 215–218 °C (decomposes).
Its UV absorbance peaks at 210 nm and 240 nm.
The presence of the C‑22‑C‑23 double bond and C‑3 hydroxyl are critical for biological activity, while the sugar moieties affect bio‑availability and membrane interaction.

Sources & Quality

Ophiopogonin D is most commonly extracted from the rhizomes of Ophiopogon japonicus (Mai Dong), cultivated in China, Japan, and Korea.
Commercial extraction uses ethanol or methanol‑water (70:30) reflux, followed by liquid‑liquid partition and C₁₈ reverse‑phase chromatography to isolate the pure saponin.
Some manufacturers employ supercritical CO₂ extraction to preserve thermolabile constituents.
Synthetic routes are rare due to the molecule’s complexity, but semi-synthetic modification of diosgenin is being explored for scale-up.
Quality considerations include verification of purity (>95 % by HPLC), absence of heavy metals, pesticide residues, and microbial contamination.
Good Manufacturing Practice (GMP) certified producers often standardize extracts to a defined Ophiopogonin D content (e.g., 0.3 % w/w) and provide certificate of analysis (CoA).
When selecting a supplement, prioritize products with third‑party testing (e.g., USP, NSF) and transparent sourcing documentation.