Natural flavonoid; Matrix Metalloproteinase-3 (MMP-3) (IC₅₀ = 32.7 μM); Matrix Metalloproteinase-9 (MMP-9) (IC₅₀ = 25.4 μM) [1]
Phosphatase and tensin homolog (PTEN) [2]

Apigenin-7-glucuronide selectively inhibited MMP-3 and MMP-9 activities with IC₅₀ values of 32.7 μM and 25.4 μM, respectively, while showing weak effects on MMP-1 and MMP-2 (IC₅₀ >100 μM). Molecular docking revealed its binding to the S1' pocket of MMP-3 via hydrogen bonds with Glu202 and Leu164. [1]

In human renal cancer cells (786-O and A498), Apigenin-7-glucuronide (20–80 μM) dose-dependently suppressed proliferation (IC₅₀ ≈ 60 μM at 48h) and migration. It upregulated PTEN expression by 2.5-fold, leading to inhibition of PI3K/Akt pathway (reduced p-Akt levels) and induction of apoptosis (increased Bax/Bcl-2 ratio and caspase-3 activation). [2]

Matrix metalloproteinase (MMP) activity can be inhibited by Apigenin-7-Oglucuronide, with IC50 values of 12.87, 22.39, 17.52, and 0.27 μM for MMP-3, MMP-8, MMP-9, and MMP-13, respectively [1]. Additionally, ACHN and 786-O cells' capacity to migrate was decreased by scutellarin A in a dose-dependent manner. Additionally, studies reveal that following a 24-hour course of treatment with scutellarin A (30, 60, and 90 μM), ACHN and 786-O cell apoptosis rates rose noticeably in a dose-dependent way as compared to the control group [2].

MMP inhibition assays used fluorogenic substrates (e.g., MCA-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH₂ for MMP-3). Recombinant MMPs were incubated with Apigenin-7-glucuronide and substrates in assay buffer (50 mM Tris-HCl, 150 mM NaCl, 10 mM CaCl₂, pH 7.5). Fluorescence intensity was measured at excitation/emission 328/393 nm to calculate enzyme activity. [1]

Metalloproteases are a family of zinc-containing endopeptidases involved in a variety of pathological disorders. The use of flavonoid derivatives as potential metalloprotease inhibitors has recently increased.Particular plants growing in Sicily are an excellent yielder of the flavonoids luteolin, apigenin, and their respective glycoside derivatives (7-O-rutinoside, 7-O-glucoside, and 7-O-glucuronide).The inhibitory activity of luteolin, apigenin, and their respective glycoside derivatives on the metalloproteases MMP-1, MMP-3, MMP-13, MMP-8, and MMP-9 was assessed and rationalized correlating in vitro target-oriented screening and in silico docking.The flavones apigenin, luteolin, and their respective glucosides have good ability to interact with metalloproteases and can also be lead compounds for further development. Glycones are more active on MMP-1, -3, -8, and -13 than MMP-9. Collagenases MMP-1, MMP-8, and MMP-13 are inhibited by compounds having rutinoside glycones. Apigenin and luteolin are inactive on MMP-1, -3, and -8, which can be interpreted as a better selectivity for both -9 and -13 peptidases. The more active compounds are apigenin-7-O-rutinoside on MMP-1 and luteolin-7-O-rutinoside on MMP-3. The lowest IC50 values were also found for apigenin-7-O-glucuronide, apigenin-7-O-rutinoside, and luteolin-7-O-glucuronide. The glycoside moiety might allow for a better anchoring to the active site of MMP-1, -3, -8, -9, and -13. Overall, the in silico data are substantially in agreement with the in vitro ones (fluorimetric assay). [1]

Antiproliferation: Renal cancer cells were treated with Apigenin-7-glucuronide (20–80 μM) for 24–72h. Viability was assessed by MTT assay; IC₅₀ values were calculated from dose-response curves. [2]

Migration assay: Cells were seeded in transwell chambers. Apigenin-7-glucuronide (40 μM) was added to the upper chamber. Migrated cells were stained and counted after 24h. [2]

Western blot: Treated cells were lysed, and proteins (PTEN, p-Akt, Akt, Bax, Bcl-2, cleaved caspase-3) were separated by SDS-PAGE, transferred to membranes, and detected with specific antibodies. [2]

[1]. Correlating In Vitro Target-Oriented Screening and Docking: Inhibition of Matrix Metalloproteinases Activities by Flavonoids. Planta Med. 2017 Jul;83(11):901-911.

[2]. Scutellarin inhibits human renal cancer cell proliferation and migration via upregulation of PTEN. Biomed Pharmacother. 2018 Nov;107:1505-1513.

Apigenin-7-glucuronide binds to MMP-3/9 catalytic domains through hydrophobic interactions and hydrogen bonding, explaining its selective inhibition profile. [1]

The antitumor effect of Apigenin-7-glucuronide in renal cancer is mediated by PTEN upregulation, which inactivates PI3K/Akt signaling and triggers mitochondrial apoptosis. [2]

Apigenin 7-glucuronide is a member of flavonoids and a glucosiduronic acid.
Apigenin 7-glucuronide has been reported in Acanthus ilicifolius, Acanthus ebracteatus, and other organisms with data available.

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Background: Scutellarin is a naturally flavone glycoside that has been shown to exhibit anti-proliferative and anti-apoptotic activities among various human malignancies. However, the anti-cancer effect of Scutellarin in Renal cell carcinoma (RCC) and the underlying mechanism remains unclear. Methods and materials: RCC cell lines ACHN and 786-O were treated with different concentrations (0-210 μM) of Scutellarin in vitro. Cell viability and proliferation were investigated by MTT and colony formation assays. Cell invasion and migration were detected by Transwell assays. Cell apoptosis and cell cycle distribution was measured by flow cytometry. Western blot was used to investigate the expression levels of crucial proteins. Xenograft tumor model was established to evaluate tumor growth in vivo. Results: Scutellarin significantly inhibited RCC cell proliferation in a dose- and time- dependent manner. Treatment of RCC cells with Scutellarin (30, 60, and 90 μM) markedly induced apoptosis and cell cycle arrested at G0/G1 phase in a concentration-dependent characteristic. Cell invasion and migration capacities of RCC cells were also dose-dependently suppressed by Scutellarin treatment. Western blot assays revealed that the crucial proteins including cyclin D1, CDK2, Bcl2, MMP-2, and MMP-9 were significantly reduced while Bax, cleaved caspase 3 and p21 were increased by Scutellarin in RCC cells. In vivo assay indicated that Scutellarin possessed anti-cancer effect on xenograft without triggering toxic effect. Mechanically, Scutellarin dramatically increased the protein level of phosphatase and tensin homologue (PTEN) and inhibited the activity of P13K/AKT/mTOR signaling. Ectopic expression of PTEN enhanced the inhibitory effect of Scutellarin on RCC proliferation while knockdown of PTEN abrogated it through regulating its downstream P13K/AKT/mTOR signaling pathway. Conclusion: Scutellarin inhibited RCC cell proliferation and invasion partially by enhancing the expression of PTEN through inhibition of P13K/AKT/mTOR pathway, suggesting that Scutellarin might serve as a potential therapeutic agent in RCC treatment. [2]

C21H18O11

446.3610

446.084

C, 56.51; H, 4.06; O, 39.43

29741-09-1

5319484

White to yellow solid powder

1.7±0.1 g/cm3

841.8±65.0 °C at 760 mmHg

>300℃

299.0±27.8 °C

0.0±3.3 mmHg at 25°C

1.740

-0.55

6

11

4

32

746

5

C1=CC(=CC=C1C2=CC(=O)C3=C(C=C(C=C3O2)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)C(=O)O)O)O)O)O)O

JBFOLLJCGUCDQP-ZFORQUDYSA-N

InChI=1S/C21H18O11/c22-9-3-1-8(2-4-9)13-7-12(24)15-11(23)5-10(6-14(15)31-13)30-21-18(27)16(25)17(26)19(32-21)20(28)29/h1-7,16-19,21-23,25-27H,(H,28,29)/t16-,17-,18+,19-,21+/m0/s1

(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyoxane-2-carboxylic acid

Apigenin 7-O-glucuronide; 29741-09-1; Apigenin-7-glucuronide; Apigenin 7-glucuronide; apigenin-7-o-glucuronide; Scutellarin A; APIGENIN-7-O-GLUCRONIDE; (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyoxane-2-carboxylic 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)

DMSO : ~250 mg/mL (~560.09 mM)

Solubility in Formulation 1: ≥ 2.17 mg/mL (4.86 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 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.66 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 20.8 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 3: ≥ 2.08 mg/mL (4.66 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 20.8 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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 (Please use freshly prepared in vivo formulations for optimal results.)