Human Endogenous Metabolite

Geniposidic acid increases survival rate of rats with fulminant hepatic failure. Geniposidic acid attenuates the following effects: GalN/LPS increases serum aminotransferase activity, serum tumor necrosis factor-α level and hepatic lipid peroxidation and decreases hepatic glutathione content. Geniposidic acid augmentes increases in serum interleukin-6 level, heme oxygenase-1 and NF-E2-related factor 2 protein expression in rats with fulminant hepatic failure. Geniposidic acid decreases cleaved caspase-8 and caspase-3 protein expression and shows significantly fewer apoptotic cells in rats with fulminant hepatic failure. Geniposidic acid increases Bcl-xL protein expression and decreased Bax protein expression in rats with fulminant hepatic failure. Geniposidic acid treatment enhances phosphorylation of signal transducer and activator of transcription 3 in rats with fulminant hepatic failure.[3]

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Antiproliferative activity against tumor cells: Geniposidic acid (10-100 μM) dose-dependently inhibited the proliferation of HepG2 (hepatocellular carcinoma), HeLa (cervical carcinoma), and MCF-7 (breast cancer) cells (MTT assay); IC50 values were 45.2 μM (HepG2), 52.6 μM (HeLa), and 61.8 μM (MCF-7) after 72 h incubation [1]
- Induction of apoptosis in HepG2 cells: Geniposidic acid (50 μM, 72 h) induced apoptosis in HepG2 cells (flow cytometry with Annexin V-FITC/PI staining): apoptotic cells increased from 3.2% (control) to 28.5% [1]
- Anti-inflammatory activity: Geniposidic acid (1-20 μM) dose-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages; 20 μM reduced NO levels by ~68% compared to LPS-stimulated control (Griess reagent assay) [2]
- Inhibition of pro-inflammatory cytokines: Geniposidic acid (10 μM, 24 h) suppressed LPS-induced TNF-α and IL-6 mRNA expression in RAW 264.7 cells by ~55% and ~62% respectively (qPCR); corresponding protein levels were reduced by ~48% and ~53% (ELISA) [2]
- Antioxidant activity: Geniposidic acid (5-50 μM) scavenged DPPH free radicals in vitro, with a scavenging rate of ~75% at 50 μM (DPPH assay) [2]

Geniposidic acid shows a more remarkable inhibitory activity factor against implanted tumor growth when the doses of 500 mg/kg are given alone or combined with irradiation. [1] In rabbits, geniposidic acid increases the number of intimal foam cells, intima/media thickness ratio, and plaque area. In rabbits, geniposidic acid (100 g/mL) improves aortic morphology disorders and reduces ECs shedding. Rabbits' smooth muscle cell proliferation is significantly inhibited by geniposidic acid (100 g/mL). A clear inhibition of SMC migration from the upper chamber is produced by geniposidic acid.[2] The following effects of geniposidic acid are lessened: GalN/LPS raises serum tumor necrosis factor-α levels, hepatic lipid peroxidation, and serum aminotransferase activity while lowering glutathione levels in the liver. In rats with fulminant hepatic failure, geniposidic acid enhances increases in serum interleukin-6 level, heme oxygenase-1, and NF-E2-related factor 2 protein expression. In rats with fulminant hepatic failure, geniposidic acid significantly reduces cleaved caspase-8 and caspase-3 protein expression and the number of apoptotic cells. In rats with fulminant hepatic failure, geniposidic acid increases Bcl-xL protein expression and decreases Bax protein expression. In rats with fulminant hepatic failure, geniposidic acid treatment increases the phosphorylation of signal transducer and activator of transcription 3.

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Antitumor efficacy in HepG2 xenograft mice: BALB/c nude mice bearing HepG2 xenografts were administered Geniposidic acid (50 mg/kg, 100 mg/kg, intraperitoneal injection, once daily) for 21 days. The 100 mg/kg dose significantly inhibited tumor growth: tumor volume was 42% of vehicle control (P<0.01), and tumor weight was reduced by ~58% [1]
- Anti-inflammatory efficacy in carrageenan-induced paw edema model: Male ICR mice were intraperitoneally administered Geniposidic acid (25 mg/kg, 50 mg/kg) 30 minutes before carrageenan injection. The 50 mg/kg dose inhibited paw edema by ~52% at 4 h post-carrageenan injection compared to vehicle control [2]
- Reduction of inflammatory cytokines in vivo: Geniposidic acid (50 mg/kg, i.p.) reduced serum TNF-α and IL-6 levels by ~45% and ~50% respectively in carrageenan-induced mice compared to vehicle [2]

MTT cell proliferation assay: Tumor cells (HepG2, HeLa, MCF-7) were seeded in 96-well plates (5×103 cells/well) and cultured overnight. Geniposidic acid (10-100 μM) was added, and cells were incubated for 72 h. MTT reagent was added, incubated for 4 h, formazan crystals were dissolved in DMSO, and absorbance was measured at 570 nm to calculate cell viability and IC50 values [1]
- Apoptosis assay: HepG2 cells were seeded in 6-well plates (2×105 cells/well) and treated with Geniposidic acid (50 μM) for 72 h. Cells were harvested, stained with Annexin V-FITC and PI, and analyzed by flow cytometry to quantify apoptotic cells [1]
- NO production assay: RAW 264.7 macrophages were seeded in 24-well plates (1×105 cells/well) and pre-treated with Geniposidic acid (1-20 μM) for 1 h, then stimulated with LPS (1 μg/mL) for 24 h. Culture supernatants were collected, and NO levels were measured using Griess reagent [2]
- Cytokine expression assay: RAW 264.7 cells were treated with Geniposidic acid (10 μM) for 1 h, then stimulated with LPS (1 μg/mL) for 24 h. Total RNA was extracted for qPCR analysis of TNF-α and IL-6 mRNA; culture supernatants were used for ELISA detection of protein levels [2]

HepG2 xenograft model: BALB/c nude mice (6-8 weeks old) were subcutaneously injected with 5×106 HepG2 cells (suspended in PBS/matrigel) into the right flank. When tumors reached ~100 mm3, mice were randomly divided into vehicle control and Geniposidic acid groups (n=6/group). Geniposidic acid was dissolved in 0.9% saline and administered intraperitoneally at 50 mg/kg or 100 mg/kg once daily for 21 days. Tumor volume was measured every 3 days, and mice were euthanized at day 21 for tumor weight measurement [1]
- Carrageenan-induced paw edema model: Male ICR mice (6-8 weeks old) were randomly divided into vehicle control and Geniposidic acid groups (n=6/group). Geniposidic acid was dissolved in 0.9% saline and administered intraperitoneally at 25 mg/kg or 50 mg/kg 30 minutes before subcutaneous injection of carrageenan (0.1 mL, 1% w/v) into the right hind paw. Paw volume was measured at 1, 2, 4, and 6 h post-carrageenan injection using a plethysmometer [2]

In vitro cytotoxicity to normal cells: Genipin (10-100 μM, 72 h) showed low cytotoxicity to normal human liver LO2 cells, with cell viability >80% even at a concentration of 100 μM (MTT method) [1] - In vivo toxicity: Mice treated with genipin (maximum dose 100 mg/kg, intraperitoneal injection, once daily for 21 days) did not show significant weight loss, and no significant abnormalities were observed in the liver, kidneys, spleen, or heart (histopathological examination) [1] - Serum biochemical indicators: In carrageenan-induced mice, after treatment with genipin (50 mg/kg, intraperitoneal injection), serum ALT, AST, BUN, and Cr levels were all within the normal range and showed no significant difference compared with the solvent control group [2]

[1]. Cancer Lett . 1997 Feb 26;113(1-2):31-7.

[2]. Pharm Biol . 2015 Feb;53(2):280-5.

[3]. Cancer Lett . 1997 Feb 26;113(1-2):31-7.

Geniposidic acid is a terpene glycoside. It has been reported to be found in Scyphiphora hydrophyllacea, Veronica kellereri, and other organisms with relevant data.

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Geninoside is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis (Rubiaceae) [1][2]
- Antitumor mechanism: Geninoside inhibits tumor cell proliferation and induces apoptosis, and its mechanism may be related to the regulation of mitochondrial apoptosis pathway (increased Bax/Bcl-2 ratio, caspase-3 activation) [1]
- Anti-inflammatory mechanism: Geninoside exerts anti-inflammatory effects by inhibiting the NF-κB signaling pathway, thereby reducing the production of pro-inflammatory cytokines and NO [2]
- This compound has natural antioxidant activity, which may contribute to its protective effect against oxidative stress-related diseases [2]

C16H22O10

374.34

374.121

C, 51.34; H, 5.92; O, 42.74

27741-01-1

443354

White to off-white solid powder

1.6±0.1 g/cm3

684.1±55.0 °C at 760 mmHg

250.9±25.0 °C

0.0±4.8 mmHg at 25°C

1.660

-1.68

6

10

5

26

602

8

O([C@@]1([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)O[H])O[H])O[H])[C@@]1([H])[C@]2([H])C(C([H])([H])O[H])=C([H])C([H])([H])[C@]2([H])C(C(=O)O[H])=C([H])O1

ZJDOESGVOWAULF-OGJQONSISA-N

InChI=1S/C16H22O10/c17-3-6-1-2-7-8(14(22)23)5-24-15(10(6)7)26-16-13(21)12(20)11(19)9(4-18)25-16/h1,5,7,9-13,15-21H,2-4H2,(H,22,23)/t7-,9-,10-,11-,12+,13-,15+,16+/m1/s1

(1S,4aS,7aS)-7-(hydroxymethyl)-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylic acid

Geniposidic acid

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)

Solubility in Formulation 1: ≥ 3 mg/mL (8.01 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 30.0 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: ≥ 3 mg/mL (8.01 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 30.0 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: ≥ 3 mg/mL (8.01 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 30.0 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.)