Ginsenoside Rh1 targets multiple cellular pathways and receptors. It acts as a weak phytoestrogen by binding and activating the estrogen receptor (ER) at approximately 50 μM. It inhibits the expression of PPAR-γ, TNF-α, IL-6, and IL-1β. It inhibits MAPK and PI3K/Akt signaling pathways and downstream transcription factors such as NF-κB and AP-1. It shows minimal activity at glucocorticoid, androgen, or retinoic acid receptors. It also has membrane-stabilizing action and enhances neuronal survival in vivo.

It was investigated how ginsenoside Rh1 affected 3T3-L1 cell adipogenesis. Lipid content in 3T3-L1 adipocytes and Oil Red O staining were used to measure how well ginsenoside Rh1 prevented adipogenesis. At 50 μM and 100 μM concentrations, ginsenoside Rh1 reduced lipogenesis by 50% and 63%, respectively. Determine the levels of expression for genes specific to adipocytes, such as PPAR-γ, C/EBP-α, FAS, and aFABP, as well as early-stage differentiation genes, such Pref-1, C/EBP-δ, and glucocorticoid receptor (GR). Following ginsenoside Rh1 treatment of 3T3-L1 cells, the mRNA of PPAR-γ, C/EBP-α, FAS, and aFABP was extracted at 18 and 24 hours, along with the mRNA of Pref-1, C/EBP-δ, and GR. Next, RT-PCR was used to examine the expression profile of genes specific to adipocytes. When compared to unstimulated adipocytes, the expression of PPAR-γ, C/EBP-α, FAS, and aFABP was considerably higher in DMI-stimulated differentiated adipocytes. On the other hand, whereas Pref-1 and C/EBP expression levels considerably decreased, treatment with DMI in the presence of ginsenoside Rh1 significantly inhibited the expression levels of PPAR-γ, C/EBP-α, FAS, and aFABP in a dose-dependent way. decline. There is no impact on δ and GR [1].

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In Vitro: Ginsenoside Rh1 (50 μM and 100 μM) significantly inhibited adipogenesis in 3T3‑L1 cells as assessed by Oil Red O staining and lipid droplet extraction, with inhibition rates of 50% and 63%, respectively [1].
Ginsenoside Rh1 at 50 μM and 100 μM suppressed the mRNA expression levels of peroxisome proliferator‑activated receptor γ (PPAR‑γ), CCAAT/enhancer‑binding protein α (C/EBP‑α), fatty acid synthase (FAS), and adipocyte fatty acid‑binding protein (aFABP) in differentiated 3T3‑L1 adipocytes, as determined by RT‑PCR [1].
Ginsenoside Rh1 at concentrations up to 150 μM did not affect the viability of 3T3‑L1 cells (crystal violet staining) [1].
In vitro, ginsenoside Rh1 inhibits adipogenesis in 3T3-L1 cells; at 50 μM and 100 μM concentrations, it reduced lipogenesis by 50% and 63%, respectively. It significantly inhibits the mRNA expression of adipocyte-specific genes PPAR-γ, C/EBP-α, FAS, and aFABP in a dose-dependent manner. It exhibits anti-inflammatory effects by suppressing mast cell degranulation and anaphylaxis, and inhibits the migration and invasion of hepatocellular carcinoma cells. It also shows antiallergic action originating from cell membrane-stabilizing and anti-inflammatory activities.

Over the course of eight weeks, mice fed a high-fat diet (HFD) gained significantly more weight in their bodies and epididyma than mice fed a low-fat diet (LFD). However, when mice fed a high-fat diet were treated with ginsenoside Rh1, the increase in body and epididymal fat weight was significantly reduced compared with mice fed a high-fat diet. Blood levels of total cholesterol, HDL, glucose, and TG were significantly higher in the HFD-fed mouse group than they were in the LFD-fed mice group. Treatment of HFD-fed mice with ginsenoside Rh1 alone can significantly lower TG levels [1].
In Vivo: Oral administration of Ginsenoside Rh1 (20 mg/kg/d) to high‑fat diet (HFD)‑fed C57BL/6J mice for 4 weeks significantly suppressed body weight gain (from 8.94 g in HFD group to 3.77 g in HFD+Rh1 group) and epididymal fat weight (from 2.14 g to 1.78 g) [1].
Ginsenoside Rh1 significantly lowered plasma triglyceride levels (from 136.53 mg/dL in HFD group to 79.45 mg/dL in HFD+Rh1 group) but did not significantly affect glucose, insulin, total cholesterol or HDL levels [1].
Ginsenoside Rh1 reduced the size and number of enlarged epididymal adipocytes as shown by hematoxylin‑eosin staining [1].
Ginsenoside Rh1 inhibited the protein and mRNA expression of PPAR‑γ, C/EBP‑α, FAS, and aFABP in epididymal fat tissue (immunoblotting and real‑time PCR) [1].
Ginsenoside Rh1 down‑regulated the expression of macrophage markers CD68 and F4/80, and pro‑inflammatory cytokines TNF‑α, IL‑1β and IL‑6 in epididymal fat tissue (real‑time PCR) and also reduced blood levels of TNF‑α, IL‑1β and IL‑6 (ELISA) [1].
Mice treated with Ginsenoside Rh1 did not show any toxicity [1].
In vivo, ginsenoside Rh1 enhances memory and learning, increasing neuronal survival. In high-fat diet (HFD)-fed mice, treatment with ginsenoside Rh1 significantly reduced body weight gain and epididymal fat weight compared to HFD-fed controls. It significantly lowered serum triglyceride (TG) levels in HFD-fed mice. It decreases adipocyte differentiation, body weight, and triglyceride levels. The compound is orally active and shows stereoselective pharmacokinetics with a 3.2-fold AUC difference between 20(S)-Rh1 and 20(R)-Rh1 epimers in vivo.

The in vitro enzyme/receptor binding assay for ginsenoside Rh1 typically involves competitive binding assays using estrogen receptor (ER) preparations. Receptor binding is assessed by incubating varying concentrations of Rh1 with ER in the presence of a radiolabeled ligand (e.g., [³H]-estradiol) at 4°C for 12-16 hours. Bound and free ligands are separated by charcoal-dextran or filtration methods, and radioactivity is counted. IC50 values are calculated from dose-response curves. For PPAR-γ binding, similar competitive binding assays using [³H]-rosiglitazone and PPAR-γ protein can be employed.

Cell Assay: Mouse embryo fibroblast 3T3‑L1 cells were cultured in DMEM containing 10% fetal bovine serum and 1% antibiotics at 37°C in a 5.6% CO2 atmosphere. Two days after confluence (designated day 0), preadipocytes were induced to differentiate in differentiation medium (DM) consisting of DMEM, 10% FBS, 1% antibiotics, 0.28 unit/mL insulin, 0.5 mM isobutylmethylxanthine and 1 μM dexamethasone for 2 days in the presence or absence of Ginsenoside Rh1 (50 or 100 μM). Cells were then switched to DM containing 10% FBS and 10 μg/mL insulin, and thereafter changed to DMEM with 10% FBS every 2 days [1].
Oil Red O staining: On day 8, cells were washed with PBS, fixed with 4% paraformaldehyde for 1 h, washed with water, stained with Oil Red O solution (6 parts 0.6% Oil Red O in isopropanol and 4 parts water) for 1 h, washed, and dried. Stained lipid droplets were dissolved in 100% isopropanol for 10 min and absorbance measured at 500 nm for quantification [1].
RT‑PCR: Total RNA was extracted from 3T3‑L1 cells using a total RNA extraction kit. cDNA was synthesized from 2 μg total RNA with oligo‑dT primers and reverse transcriptase. PCR reactions were performed using Premix EX Taq with specific primers for PPAR‑γ, C/EBP‑α, FAS, aFABP, and GAPDH. Cycling conditions: denaturation at 94°C for 30 s, annealing at appropriate temperatures (50‑60°C) for 30 s, extension at 72°C for 1 min, with varying cycles. Products were resolved on 2% agarose gels and visualized under UV [1].
Cell viability was assessed by crystal violet staining (no further details provided) [1].
In vitro cell-based assays for ginsenoside Rh1 typically use 3T3-L1 preadipocytes to study adipogenesis inhibition. Cells are differentiated using a cocktail containing DMI (dexamethasone, isobutylmethylxanthine, insulin) for 48 hours, then maintained in insulin-containing medium. Rh1 is added at various concentrations (e.g., 10-100 μM) during differentiation. Lipid accumulation is assessed by Oil Red O staining and quantified spectrophotometrically at 490 nm. Gene expression of PPAR-γ, C/EBP-α, FAS, and aFABP is analyzed by RT-PCR at 18 and 24 hours. Cytotoxicity is evaluated using MTT assays (LC₅₀ = 210 μg/mL in THP-1 cells).

Animal Protocol: Male C57BL/6J mice (4 weeks old) were acclimated for 3 days and then fed either a low‑fat diet (LFD, 10% calories from fat) or a high‑fat diet (HFD, 60% calories from fat) for 8 weeks. Mice were divided into three groups (n=10 each): LFD group (LFD for 8 weeks), HFD group (HFD for 8 weeks), and HFD‑Rh1 group (HFD for 4 weeks, then HFD plus oral administration of Ginsenoside Rh1 at 20 mg/kg/day for another 4 weeks). Body weight and food intake were measured daily. After 4 weeks of treatment, mice were sacrificed; blood and epididymal fat pads were collected. For histological analysis, epididymal fat pads were fixed in 4% paraformaldehyde, dehydrated in graded ethanol, embedded in paraffin, sectioned at 7 μm thickness, and stained with hematoxylin‑eosin for microscopic examination. All procedures followed NIH and institutional guidelines for animal care [1].
In vivo animal studies with ginsenoside Rh1 typically use mouse models. For obesity studies, male C57BL/6 mice are fed a high-fat diet (HFD) for 8 weeks to induce obesity. Rh1 is administered orally or intraperitoneally at doses ranging from 10-50 mg/kg daily for 4-8 weeks. Body weight, food intake, and epididymal fat weight are measured. Blood samples are collected for analysis of total cholesterol, HDL, glucose, and triglycerides. For memory studies, Morris water maze or novel object recognition tests are performed. Tissue samples (liver, adipose) are collected for histological analysis and gene expression studies.

Ginsenoside Rh1 shows stereoselective pharmacokinetics with a 3.2-fold AUC difference between 20(S)-Rh1 and 20(R)-Rh1 epimers in vivo. It is orally active. As a monoglucosylated metabolite rather than a native abundant ginsenoside, Rh1 exhibits distinct bioavailability and receptor interaction profiles compared to its multi-glycosylated precursors. The compound has a molecular weight of 638.9 g/mol and is soluble in DMSO. Storage: dry, dark at 0-4°C for short term or -20°C for long term.

Toxicity/Toxicokinetics: In the mouse study, Ginsenoside Rh1 (20 mg/kg/day oral for 4 weeks) did not show any toxicity; treated mice exhibited normal behavior and no adverse effects were reported [1].
In vitro, Ginsenoside Rh1 at concentrations up to 150 μM did not affect 3T3‑L1 cell viability as assessed by crystal violet staining [1].
Ginsenoside Rh1 shows minimal cytotoxicity with an LC₅₀ of 210 μg/mL in THP-1 cells, enabling extended treatment windows up to 72 hours. It is supplied as an analytical reference standard with purity typically ≥95% to ≥98%. It has antiallergic action originating from its cell membrane-stabilizing and anti-inflammatory activities. It can improve inflammation caused by allergies. It inhibits MAPK and PI3K/Akt signaling pathways and downstream transcription factors such as NF-κB and AP-1.

[1]. Ginsenoside Rh1 ameliorates high fat diet-induced obesity in mice by inhibiting adipocyte differentiation. Biol Pharm Bull. 2013;36(1):102-7.

(20S)-Ginsenoside Rh1 is a tetracyclic triterpenoid compound with the structure (20S)-protopanaxadiol, where the 6α-position is replaced by β-D-glucoside. It is a plant metabolite. It is a β-D-glucoside, 12β-hydroxysterol, tetracyclic triterpenoid, ginsenoside, 3β-hydroxysterol, and 3β-hydroxy-4,4-dimethylsterol. It is derived from the hydride of dammarane. Ginsenoside Rh1 has been reported to exist in ginseng, Gynostemma pentaphyllum, and other organisms with relevant data.

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Additional Info: Ginsenoside Rh1 is a protopanaxatriol‑type ginsenoside. It is a metabolite of ginsenosides Re and Rg1 produced by human intestinal microflora. It has previously been reported to possess anti‑allergic, anti‑inflammatory and estrogenic activities. This study demonstrates that Ginsenoside Rh1 ameliorates high‑fat diet‑induced obesity by inhibiting adipocyte differentiation (via down‑regulation of PPAR‑γ, C/EBP‑α, FAS, aFABP) and by reducing inflammation (via suppression of TNF‑α, IL‑1β, IL‑6 and macrophage infiltration). Unlike protopanaxadiol ginsenoside Rh2, which has been studied in vitro for anti‑adipogenic effects, Ginsenoside Rh1 showed in vivo efficacy in obesity models [1].
Ginsenoside Rh1 is a natural product isolated from Panax ginseng used primarily for research purposes. It is not approved as a therapeutic drug but is extensively studied for its potential health benefits. The compound's anti-inflammatory, anti-adipogenic, and neuroprotective properties make it a subject of interest for metabolic disorders, neurodegenerative diseases, and inflammatory conditions. It is available as a research-grade compound with high purity (≥98% HPLC). This product is for research use only, not for human use.

C36H62O9

638.883

638.439

63223-86-9

(20R)-Ginsenoside Rh1;80952-71-2

12855920

White to off-white solid powder

1.2±0.1 g/cm3

755.1±60.0 °C at 760 mmHg

410.5±32.9 °C

0.0±5.7 mmHg at 25°C

1.581

3.74

7

9

7

45

1110

16

CC(=CCC[C@@](C)([C@H]1CC[C@@]2([C@@H]1[C@@H](C[C@H]3[C@]2(C[C@@H]([C@@H]4[C@@]3(CC[C@@H](C4(C)C)O)C)O[C@H]5[C@@H]([C@H]([C@@H]([C@H](O5)CO)O)O)O)C)O)C)O)C

RAQNTCRNSXYLAH-RFCGZQMISA-N

InChI=1S/C36H62O9/c1-19(2)10-9-13-36(8,43)20-11-15-34(6)26(20)21(38)16-24-33(5)14-12-25(39)32(3,4)30(33)22(17-35(24,34)7)44-31-29(42)28(41)27(40)23(18-37)45-31/h10,20-31,37-43H,9,11-18H2,1-8H3/t20-,21+,22-,23+,24+,25-,26-,27+,28-,29+,30-,31+,33+,34+,35+,36-/m0/s1

(2R,3R,4S,5S,6R)-2-[[(3S,5R,6S,8R,9R,10R,12R,13R,14R,17S)-3,12-dihydroxy-17-[(2S)-2-hydroxy-6-methylhept-5-en-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-6-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol

ginsenoside Rh1 CS-3834 CS3834Prosapogenin A2 Sanchinoside B2 Sanchinoside Rh1

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~156.53 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)