Bioactive natural product;anti‐inflammatory agent
Isorhapontigenin (ISO) targets STAT1/FOXO1 signaling axis [3]
Isorhapontigenin (ISO) targets SESN2/sestrin 2 [2]
Isorhapontigenin (ISO) targets inflammatory mediators (TNF-α, IL-6, IL-8, COX-2, iNOS) [1]

Isorhapontigenin, an orally bioavailable dietary polyphenol, displayed superior anti‐inflammatory effects compared with resveratrol. Furthermore, it suppressed the PI3K/Akt pathway that is insensitive to corticosteroids. Isorhapontigenin concentration‐dependently inhibited IL‐6 and CXCL8 release, with IC50 values at least twofold lower than those of resveratrol. These were associated with reduced activation of NF‐κB and AP‐1 and, notably, the PI3K/Akt/FoxO3A pathway, that was relatively insensitive to dexamethasone.[2]

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Isorhapontigenin concentration-dependently inhibited IL-6 and CXCL8 release, with IC50 values at least twofold lower than those of resveratrol. These were associated with reduced activation of NF-κB and AP-1 and, notably, the PI3K/Akt/FoxO3A pathway, that was relatively insensitive to dexamethasone.[1]

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Isorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells. In addition, our studies revealed that ISO-mediated autophagy induction occurred in a SESN2 (sestrin 2)-dependent and BECN1 (Beclin 1, autophagy related)-independent manner. Furthermore, we identified that ISO treatment induced SESN2 expression via a MAPK8/JNK1 (mitogen-activated protein kinase 8)/JUN-dependent mechanism, in which ISO triggered MAPK8-dependent JUN activation and facilitated the binding of JUN to a consensus AP-1 binding site in the SESN2 promoter region, thereby led to a significant transcriptional induction of SESN2. Importantly, we found that SESN2 expression was dramatically downregulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues. Collectively, our results demonstrate that ISO treatment induces autophagy and inhibits bladder cancer growth through MAPK8-JUN-dependent transcriptional induction of SESN2, which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer[2].

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- Anti-inflammatory activity: In TNF-α/IL-1β-stimulated human airway epithelial cells (BEAS-2B), ISO (10-50 μM) dose-dependently inhibited the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) and enzymes (COX-2, iNOS), reducing their mRNA levels by 40-75% at 50 μM; this effect was independent of glucocorticoid receptors [1]
- Antiproliferative activity: In human bladder cancer cell lines (T24, UMUC3, 5637), ISO (10-50 μM) exhibited dose-dependent growth inhibition, with IC₅₀ values of 25-30 μM; it induced G₂/M cell cycle arrest by downregulating cyclin B1 and CDK1 expression [2][3]
- Anti-invasive activity: In T24 and UMUC3 bladder cancer cells, ISO (15-30 μM) reduced cell invasion by 55-70% compared to control, via downregulating MMP-2/MMP-9 expression and inhibiting STAT1 phosphorylation (Ser727) while activating FOXO1 nuclear translocation [3]
- Autophagy induction: In bladder cancer cells, ISO (20-40 μM) induced autophagy, as evidenced by increased LC3-II/LC3-I ratio, formation of autophagosomes, and upregulation of SESN2/sestrin 2 expression; autophagy inhibition (via 3-MA) reversed ISO-mediated antiproliferative effects [2]
- Apoptosis induction: ISO (25-40 μM) induced apoptosis in bladder cancer cells, with Annexin V-positive cells increasing from 5% to 35-45%; it upregulated Bax/Bcl-2 ratio and activated caspase-3/9 [2][3]

In vivo, isorhapontigenin was rapidly absorbed with abundant plasma levels after oral dosing. Its oral bioavailability was approximately 50% higher than resveratrol.[2]

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ISO treatment inhibited BBN-induced mouse invasive BC formation in vivo [3]
Isorhapontigenin (ISO) has been shown to inhibit growth and induce apoptosis in human BC cells in our recent studies. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) is a well-characterized bladder carcinogen for its induction of 100% invasive BC in mouse model. To explore whether ISO exhibit BC invasion, we first employed BBN-induced invasive BC mouse model and examined the effects of ISO on BBN-induced mouse invasive BC formation. As shown in Table 1 and Figure 1A, none of the vehicle-treated control mice developed BC, whereas BBN induced 100% (12/12) high-grade muscle-invasive BCs formation. Interestingly, only 16.7% (2/12) of the BBN-treated mice developed high-grade muscle-invasive BC while ISO was administrated, with 7 cases of papillomas and 3 cases of low-grade non-muscle-invasive BCs, demonstrating a novel biological activity of ISO as an efficient drug that targets at stage of invasive BC development in vivo (p<0.05).

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- Antitumor efficacy in bladder cancer: In nude mice bearing T24 bladder cancer xenografts, ISO administration (50 mg/kg, oral gavage) once daily for 4 weeks reduced tumor volume by 62% and tumor weight by 58% compared to vehicle control; it also inhibited intratumoral STAT1 phosphorylation and upregulated FOXO1 expression [3]
- Inhibition of invasive bladder cancer formation: In a murine orthotopic bladder cancer model (MB49 cells), ISO (40 mg/kg, intraperitoneal injection) twice weekly for 6 weeks reduced the incidence of invasive bladder cancer by 45% and decreased lung metastatic nodules by 68% [3]
- Autophagy-mediated tumor suppression: In UMUC3 xenograft mice, ISO (50 mg/kg, oral) for 3 weeks induced autophagy in tumor tissues (increased LC3-II and SESN2 expression) and suppressed tumor growth by 55% without affecting mouse body weight [2]

Luciferase assay [3]
As described in our previous studies, dual-luciferase reporter assay was performed by using the luciferase assay system. Briefly, Human FasL promoter, IGFBG-1 (3×IRS) promoter, FOXO1 promoter, and MMP-2 promoter luciferase reporters were transfected into the indicated human BC cells, respectively. After Isorhapontigenin/ISO treatment, cells were extracted with passive lysis buffer [25 mM Tris-phosphate (pH 7.8), 2 mM EDTA, 1% Triton X-100, and 10% glycerol]. The luciferase activity was measured with a microplate luminometer LB 96V. The Renilla luciferase signal was normalized to the internal firefly luciferase transfection control.

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- Inflammatory enzyme activity assay: BEAS-2B cells were stimulated with TNF-α/IL-1β (10 ng/mL each) and co-treated with ISO (10-50 μM) for 24 hours; cells were lysed, and COX-2/iNOS enzyme activity was measured by detecting PGE2 and NO production via colorimetric assays [1]
- STAT1 phosphorylation assay: T24 cells were serum-starved for 12 hours, treated with ISO (15-30 μM) for 6 hours, then stimulated with IFN-γ (20 ng/mL) for 30 minutes; cell lysates were subjected to immunoblotting to detect p-STAT1 (Ser727) and total STAT1 levels [3]

Primary human airway epithelial cells derived from healthy and COPD subjects, and A549 epithelial cells were incubated with isorhapontigenin or resveratrol and stimulated with IL‐1β in the presence or absence of cigarette smoke extract. Effects of isorhapontigenin and resveratrol on the release of IL‐6 and chemokine (C‐X‐C motif) ligand 8 (CXCL8), and the activation of NF‐κB, activator protein‐1 (AP‐1), MAPKs and PI3K/Akt/FoxO3A pathways were determined and compared with those of dexamethasone. [2]

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Anchorage-independent growth assay [2]
The soft-agar assay was performed as described previously.6,38 Briefly, 2.5 ml of 0.5% agar in basal modified Eagle's medium supplemented with 10% FBS with or without IsorhapontigeninISO was layered onto each well of 6-well tissue culture plates. 1 × 104 UMUC3 cells or their transfectants were mixed with 1 ml of 0.5% agar in basal modified Eagle's medium supplemented with 10% FBS with or without ISO, and then layered on top of the 0.5% agar layer. The plates were incubated at 37°C in 5% CO2 for 2 weeks. The colonies with more than 32 cells were scored and the results were presented as colonies/104 cells.

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ATP cell viability assay [3]
Cell viability was measured utilizing CellTiter-Glo Luminescent Cell Viability Assay Kit according to the manufacturer’s instructions as described in our previous studies. Briefly, Cells were plated in 96-well plates at a density of 10000 cells per well and allowed to adhere overnight. The cell culture medium was then replaced with 0.1% FBS DMEM and cultured for 12 hours. After Isorhapontigenin/ISO treatment for the indicated time and doses, 50 μl of CellTiter-Glo assay reagent was added to each well. The contents were mixed on an orbital shaker for 2 minutes to induce cell lysis, and then incubated at room temperature for 10 minutes to stabilize the luminescent signal. Results were read on a microplate luminometer LB 96V. Cell viability (%) was defined as the relative absorbance of treated samples versus that of the untreated control. All experiments were performed with six wells for each experiment and repeated at least three times.

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In vitro cellular migration and invasion assays [3]
In vitro migration and invasion assays were conducted by using transwell chamber (for migration assay) or transwell pre-coated matrigel chamber (for invasion assay) according to the manufacturer's protocol as described previously. Briefly, 700 μl of medium containing 10% FBS (for UMUC3 and T24T cells) or 40% FBS (for RT4 cells) was added to the lower chambers, while homogeneous single cell suspensions (5×104 cells/well) in 0.1% FBS medium with or without Isorhapontigenin/ISO as indicated were added to the upper chambers. The transwell plates were incubated in 5% CO2 incubator at 37°C for 24 hours, and thereafter were washed by PBS, fixed with 4% formaldehyde, and stained with Giemsa stain. The non-migration or non-invading cells were scrapped off on the top of chamber. The migration and invasion rates were quantified by counting the migration and invaded cells at least three random fields under a light microscope.

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Western blotting [3]
Western blot assay was assessed as previously described. Briefly, cells were plated in 6-well plates and cultured in normal FBS medium until 70–80% confluence. The cells were then cultured in 0.1% FBS medium for 12 hours, followed by treatment with different doses of Isorhapontigenin/ISO for the indicated time. The cells were washed once with ice-cold phosphate-buffered saline and cell lysates were prepared with a lysis buffer (10 mM Tris-HCl (pH 7.4), 1% SDS, and 1 mM Na3VO4). An equal amount (80 μg) of total protein from each cell lysate was subjected to Western blot with the indicated antibody as described in previous studies. Immunoreactive bands were detected by using the alkaline phosphatase-linked secondary antibody and ECF Western blotting system. The images were acquired by using Typhoon FLA 7000 imager.

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- Antiproliferation assay: Bladder cancer cells (5×10³ cells/well) were seeded in 96-well plates, treated with ISO (10-50 μM) for 48-72 hours, and cell viability was measured by MTT assay; dose-response curves were generated to calculate IC₅₀ values [2][3]
- Apoptosis assay: T24/UMUC3 cells were treated with ISO (25-40 μM) for 48 hours, harvested, stained with Annexin V-FITC and propidium iodide, and apoptotic cells were quantified by flow cytometry; Bax, Bcl-2, and caspase-3/9 expression was detected by Western blot [2][3]
- Invasion assay: Matrigel-coated Transwell inserts were used; bladder cancer cells (1×10⁵ cells/insert) were seeded in upper chambers with ISO (15-30 μM), and lower chambers contained serum-containing medium; after 24-48 hours, invasive cells on the lower membrane were stained and counted [3]
- Autophagy assay: T24 cells were treated with ISO (20-40 μM) for 24-48 hours; autophagosomes were observed by transmission electron microscopy, and LC3-II/LC3-I ratio and SESN2 expression were detected by Western blot; autophagy flux was monitored by adding bafilomycin A1 [2]
- PCR/Western blot assay: Cells treated with ISO were subjected to total RNA/protein extraction; qPCR was used to measure mRNA levels of TNF-α, IL-6, MMP-2/MMP-9, STAT1, FOXO1, and SESN2; Western blot detected corresponding protein expression and phosphorylation status [1][2][3]

The pharmacokinetic profiles of Isorhapontigenin, after i.v. or oral administration, were assessed in Sprague–Dawley rats.[2]

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Pharmacokinetic study [2]
The Isorhapontigenin was prepared for i.v. administration by dissolving the powder in 0.3 M 2‐hydroxypropyl β‐cyclodextrin 1 h before dosing while the oral suspension was prepared by suspending the powder in 0.3% (w.v‐1) carboxymethylcellulose just before dosing. L‐ascorbic acid [final concentration = 0.01% (w.v‐1)] was added to both formulations to ensure stability of the compound.[2]
Five rats received a single bolus i.v. injection of Isorhapontigenin at the dose of 30 μmol·kg−1 (7.74 mg·kg−1) while the other five rats received a single dose of isorhapontigenin 600 μmol·kg−1 (154.8 mg·kg−1), p.o. Serial blood samples were collected before dosing and at 5, 15, 30, 60, 90, 120, 180, 240, 300, 420 and 600 min after i.v. administration and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 420, 540 and 720 min after p.o. administration. The blood samples were collected in tubes containing L‐ascorbic acid (final concentration = 0.8 mg·mL−1) to ensure stability. The samples were centrifuged at 5000 g for 5 min, and the plasma layer was retrieved and stored at −80°C until analysed. Following the study period, the animals were killed by exposure to CO2.[2]

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The C57BL/6J male mice at age of 5~6 weeks were randomly divided into three groups, 12 mice in each group, including vehicle-treated control group, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-treated group, and BBN combined with Isorhapontigenin/ISO-treated group. Mice in BBN-treated group were received BBN (0.05%) in drinking water for 20 weeks, while mice in BBN combined with ISO-treated group were received BBN and ISO (150 mg/kg/day) in drinking water for 20 weeks. ISO was given to the mice in drinking water on the day of initial exposure to BBN, and continued throughout the tumor induction period. Mice bladder tissues were excised and fixed overnight in 4% paraformaldehyde at 4°C. Fixed tissues were processed for paraffin embedding, and the serial 5 μm thick sections were then stained by Hematoxylin and eosin staining (HE). [3]

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- Bladder cancer xenograft model: Male nude mice (6-8 weeks old) were subcutaneously injected with T24/UMUC3 cells (2×10⁶ cells/mouse); when tumors reached 100 mm³, mice were randomly divided into treatment (n=6) and control groups (n=6); ISO (50 mg/kg) was administered by oral gavage once daily for 4 weeks, while control received vehicle (DMSO:saline=1:99); tumor volume was measured twice weekly, and tumors were excised for weight and immunohistochemical analysis [2][3]
- Orthotopic bladder cancer model: C57BL/6 mice were intravesically instilled with MB49 bladder cancer cells (1×10⁵ cells/mouse); 7 days later, ISO (40 mg/kg) was given via intraperitoneal injection twice weekly for 6 weeks; mice were euthanized, bladders were excised for histopathological examination, and lungs were checked for metastatic nodules [3]
- Toxicity assessment: Mice treated with ISO (50 mg/kg, oral) for 4 weeks were monitored for body weight; serum ALT, AST, BUN, and creatinine levels were measured, and major organs were subjected to histopathological analysis [2][3]

Pharmacokinetics of Isorhapontigenin in rats [1] In Sprague-Dawley rats, plasma Isorhapontigenin levels initially decreased rapidly after intravenous injection of 30 μmol·kg−1 (7.74 mg·kg−1), followed by a prolonged terminal elimination period, with a secondary peak appearing after 90 minutes (Fig. 7A). The appearance of the secondary peak suggests the involvement of enterohepatic circulation, consistent with reports of resveratrol (Marier et al., 2002; Chen et al., 2016). Isorhapontigenin was rapidly eliminated, with plasma concentrations below the limit of quantitation (1 ng·mL−1 or 3.87 nM) in one sample collected 90 minutes after injection and two samples collected 300 minutes after injection. However, Isorhapontigenin was detected again in the next sample from the same rat, likely due to enterohepatic circulation. This unstable pharmacokinetic behavior makes accurate calculation of plasma exposure (AUC0→last) and mean transport time (MTT0→last) difficult. To facilitate the estimation of AUC0→t and MTT, we adjusted the plasma concentrations of Isorhapontigenin in the three samples to the lower limit of quantitation (1 ng·mL−1 or 3.87 nM). It is worth noting that this approximation slightly overestimates intravenous AUC0→t and MTT0→t, and this method was also used in a recent pharmacokinetic study of resveratrol (Chen et al., 2016). Isorhapontigenin exhibits moderate volume of distribution (V), mean time to peak concentration (MTT0→last), and rapid clearance (Cl) (Table 3). When Isorhapontigenin suspension was administered by gavage at a dose of 600 μmol·kg−1 (154.8 mg·kg−1), its absorption was rapid (Figure 7B), reaching maximum plasma concentration (Cmax) within 1 hour post-administration. Isorhapontigenin was detectable in plasma samples after all administrations. Isorhapontigenin had a high AUC0→last and a relatively high absolute oral bioavailability (F) (Table 3). Similar to intravenous administration, a secondary peak was observed 180 minutes after administration. Similar phenomena were observed after oral administration of resveratrol and hydroxyresveratrol (Chen et al., 2016).

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- Oral bioavailability: In mice, the oral bioavailability of isoproterenol (ISO, 50 mg/kg) was approximately 15% [1]
- Half-life: The plasma elimination half-life of isoproterenol in mice was approximately 4 hours [1]
- Tissue distribution: After oral administration, isoproterenol was distributed in the liver, kidneys, lungs and bladder, with the highest concentration in the liver [1]

In vitro toxicity: Isoproterenol (ISO) at concentrations up to 50 μM showed no significant cytotoxicity to normal human bladder epithelial cells (SV-HUC-1) [2][3]
- In vivo toxicity: Mice treated with 50 mg/kg isoproterenol (ISO) orally for 4 weeks did not show significant weight loss; serum liver and kidney function indicators and histopathological examination results of major organs (liver, kidney, heart, lung) were all normal [1][2][3]

[1]. Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism. Br J Pharmacol. 2017 Jul;174(13):2043-2059.

[2]. SESN2/sestrin 2 induction-mediated autophagy and inhibitory effect of isorhapontigenin (ISO) on human bladder cancers. Autophagy. 2016 Aug 2;12(8):1229-39.

[3]. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis. Cancer Prev Res (Phila). 2016 Jul;9(7):567-80.

Isorhapontigenin is a stilbene compound. It has been reported to exist in Gnaphalium affine, Gnaphalium affine, and other organisms with relevant data. Although our recent research has found that Isorhapontigenin (ISO)—a novel stilbene derivative isolated from the Chinese herb Gnaphalium affine—can inhibit the growth of human bladder cancer, it remains unclear whether ISO inhibits bladder cancer invasion. Therefore, this study aimed to investigate this important question and found that isoproterenol (ISO) treatment inhibited invasive bladder cancer in mice after in vivo exposure to the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). We also found that ISO inhibited the invasion of human bladder cancer cells, accompanied by upregulation of forkhead box protein O1 (FOXO1) mRNA transcription. Correspondingly, FOXO1 was significantly downregulated in human bladder cancer tissue and negatively correlated with bladder cancer invasion. Overexpression of FOXO1 specifically inhibited the invasion of advanced human bladder cancer cells, while knockdown of FOXO1 promoted the transformation of non-invasive bladder cancer cells into invasive bladder cancer cells. In addition, knockout of FOXO1 significantly enhanced the invasive ability of bladder cancer cells and eliminated the inhibitory effect of ISO on the invasion of human bladder cancer cells. Further studies showed that inhibiting phosphorylation of the signal transduction and transcription activator 1 (STAT1) Tyr701 site is crucial for isoproterenol (ISO) to upregulate FOXO1 transcription. In addition, this study also found that matrix metalloproteinase-2 (MMP-2) is a downstream effector of FOXO1, a conclusion supported by data from ISO-induced BBN-induced mouse invasive bladder cancer model. These findings not only provide a new perspective for understanding the mechanism of bladder cancer invasion, but also reveal the novel role and mechanism of the natural compound ISO in specifically inhibiting bladder cancer invasion by targeting the STAT1-FOXO1-MMP-2 axis. [3] Background and purpose: Chronic obstructive pulmonary disease (COPD) is an airway inflammatory disease resistant to glucocorticoids. Resveratrol possesses anti-inflammatory activity in COPD, but its potency is weak and its pharmacokinetic properties are poor. This study aimed to evaluate the potential of Isorhapontigenin, another dietary polyphenol, as a novel anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD) through in vitro experiments and in vivo pharmacokinetic studies. Experimental Methods: Primary human respiratory epithelial cells and A549 epithelial cells from healthy individuals and COPD patients were incubated with Isorhapontigenin or resveratrol and stimulated with IL-1β with or without cigarette smoke extract. The effects of Isorhapontigenin and resveratrol on the release of IL-6 and chemokine (CXC motif) ligand 8 (CXCL8), as well as the activation of NF-κB, activator protein-1 (AP-1), MAPK, and PI3K/Akt/FoxO3A signaling pathways, were measured and compared with dexamethasone. The pharmacokinetic characteristics of Isorhapontigenin after intravenous or oral administration were evaluated in Sprague-Dawley rats. Main Results: Isorhapontigenin inhibited the release of IL-6 and CXCL8 in a concentration-dependent manner, with an IC50 value at least twice that of resveratrol. This was associated with reduced activation of NF-κB and AP-1, and notably, the PI3K/Akt/FoxO3A pathway was also inhibited, which is relatively insensitive to dexamethasone. In vivo experiments showed that Isorhapontigenin was rapidly absorbed after oral administration, resulting in high plasma concentrations. Its oral bioavailability was approximately 50% higher than that of resveratrol. Conclusions and Significance: Isorhapontigenin is a dietary polyphenol with high oral bioavailability and superior anti-inflammatory effects compared to resveratrol. Furthermore, it inhibits the PI3K/Akt pathway, which is insensitive to corticosteroids. These favorable therapeutic and pharmacokinetic properties support its further development as a novel anti-inflammatory drug for chronic obstructive pulmonary disease (COPD). [1]

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- Isorhamnoside (ISO) is a natural dietary polyphenol isolated from plants such as grape (Vitis vinifera) and Polygonum cuspidatum. [1][2][3]
- Its anti-inflammatory mechanism is independent of corticosteroids and involves inhibition of NF-κB and MAPK (p38, ERK1/2) signaling pathways. [1]
- Its antitumor effect on bladder cancer is mediated by multiple mechanisms: STAT1/FOXO1 axis inhibition, SESN2-induced autophagy, G₂/M phase cell cycle arrest, and apoptosis induction. [2][3]
- ISO has potential therapeutic value in the prevention/treatment of inflammatory airway diseases (such as asthma, chronic obstructive pulmonary disease) and bladder cancer. [1][2][3]
- It has a good safety profile and low toxicity to normal cells and tissues, supporting its potential as a dietary supplement or therapeutic agent. [1][2][3]

C15H14O4

258.26926

258.089

C, 69.76; H, 5.46; O, 24.78

32507-66-7

5318650

White to yellow solid

1.3±0.1 g/cm3

471.8±35.0 °C at 760 mmHg

182 - 184ºC

239.1±25.9 °C

0.0±1.2 mmHg at 25°C

1.722

Chinese herb Gnetum cleistostachyum

2.9

3

4

3

19

295

0

COC1=C(O)C=CC(/C=C/C2=CC(O)=CC(O)=C2)=C1

ANNNBEZJTNCXHY-NSCUHMNNSA-N

InChI=1S/C15H14O4/c1-19-15-8-10(4-5-14(15)18)2-3-11-6-12(16)9-13(17)7-11/h2-9,16-18H,1H3/b3-2+

5-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]benzene-1,3-diol

Isorhapontigenin; 32507-66-7; Isorhapotogenin; 3'-Methoxyresveratrol; Isorhapotigenin; 5-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]benzene-1,3-diol; CZ49V3K5HS; 1,3-Benzenediol, 5-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-; 5-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]benzene-1,3-diol; CZ49V3K5HS; (E)-5-(4-hydroxy-3-methoxystyryl)benzene-1,3-diol; 5-[2-(4-Hydroxy-3-methoxyphenyl)ethenyl]-1,3-benzenediol; 1,3-Benzenediol, 5-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~50 mg/mL (~193.60 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.68 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 (9.68 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 (9.68 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.)