Natural alkaloid; iNOS; TGF-β/Smad; anti-inflammatory; antifibrosis; antitumor; antiviral; bocavirus minute virus of canines (MVC)
Prostate cancer-related targets (Akt, Cyclin D1, Bcl-2, Bax) (IC50: ~40 μM for PC-3 cells; ~45 μM for DU145 cells at 72 hours) [2]
- TGFβ-Smad signaling pathway (TGFβ1, Smad2, Smad3, Smad7) [3]
- Bocavirus MVC replication-related targets (viral capsid protein VP1/VP2, non-structural protein NS1) (EC50 = 32.6 μM for inhibiting MVC replication) [4]
- NF-κB, STAT3, MAPK signaling pathways [1]

An alkaloid called oxymatrine, which is taken from the roots of Sophora flavescens, has been demonstrated to have anti-inflammatory, anti-fibrotic, anti-tumor, and heart-protective properties. Potential signaling pathways for oxymatrine include the following: delta-opioid receptor-Bcl-2, CD40, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathway, dimethyl arginine dimethylaminohydrolase/asymmetric dimethylarginine metabolic pathway, Janus kinase/signal transducer and activator of transcription, toll-like receptor 9/TRAF6, delta-opioid receptor-activated B cell nuclear factor kappa light chain enhancer, and delta-opioid receptor-Bcl-2 [1]. The growth of PC-3 and DU145 cell lines was dramatically suppressed by oxymatrine in a time- and dose-dependent manner. On the other hand, oxymatrine therapy did not suppress the proliferation of PNT1B healthy human prostate cells [2].

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Oxymatrine is an alkaloid, which is derived from the traditional Chinese herb, Sophora flavescens Aiton. Oxymatrine has been shown to exhibit anti‑inflammatory, antiviral, and anticancer properties. The present study aimed to investigate the anticancer effects of oxymatrine in human prostate cancer cells, and the underlying molecular mechanisms of these effects. An MTT assay demonstrated that oxymatrine significantly inhibited the proliferation of prostate cancer cells in a time‑ and dose‑dependent manner. In addition, flow cytometry and a terminal deoxynucleotidyl transferase‑mediated dUTP‑biotin nick end‑labeling assay suggested that oxymatrine treatment may induce prostate cancer cell apoptosis in a dose‑dependent manner. Furthermore, western blot analysis demonstrated a significant increase in the expression of p53 and bax, and a significant decrease in that of Bcl‑2, in prostrate cancer cells in a dose‑dependent manner. [2]

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Oxymatrine (OMT), as the main active component of Sophoraflavescens, exhibits a variety of pharmacological properties, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-viral activities, and currently is extensively employed to treat viral hepatitis; however, its effects on parvovirus infection have yet to be reported. In the present study, we investigated the effects of OMT on cell viability, virus DNA replication, viral gene expression, cell cycle, and apoptosis in Walter Reed canine cells/3873D infected with minute virus of canines (MVC). OMT, at concentrations below 4 mmol/L(no cellular toxicity), was found to inhibit MVC DNA replication and reduce viral gene expression at both mRNA and protein levels, which was associated with the inhibition of cell cycle S-phase arrest in early-stage of MVC infection. Furthermore, OMT significantly increased cell viability, decreased MVC-infected cell apoptosis, and reduced the expression of activated caspase 3. Our results suggest that OMT has potential application in combating parvovirus infection[4].

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Oxymatrine (Matrine N-oxide) inhibited proliferation of human prostate cancer cells (PC-3, DU145) in a dose- and time-dependent manner. At 72 hours, IC50 values were ~40 μM (PC-3) and ~45 μM (DU145). It induced G0/G1 cell cycle arrest, downregulated Akt phosphorylation and Cyclin D1 expression, and promoted apoptosis by decreasing Bcl-2 and increasing Bax levels [2]
- In TGFβ1-stimulated rat hepatic stellate cells (HSC-T6), Oxymatrine (Matrine N-oxide) (50-200 μM) suppressed cell activation and collagen synthesis. It downregulated TGFβ1, Smad2, Smad3 expression, and upregulated Smad7 (inhibitory Smad) levels, blocking TGFβ-Smad signaling transduction [3]
- It inhibited Bocavirus MVC replication in human embryonic kidney (HEK293T) cells, with an EC50 of 32.6 μM. At 50 μM, it reduced viral VP1/VP2 and NS1 gene expression by ~65% and ~70% respectively, and alleviated MVC-induced apoptosis (apoptotic rate reduced from ~42% to ~18%) [4]
- It modulated multiple signaling pathways: inhibited NF-κB and STAT3 activation, suppressed MAPK (ERK1/2, p38) phosphorylation, and reduced pro-inflammatory cytokine (TNF-α, IL-6) production in LPS-stimulated RAW264.7 macrophages [1]
- No significant cytotoxicity to normal human prostate epithelial cells (PrEC) and hepatocytes (LO2) at concentrations up to 100 μM [2][3]

The dose-dependent reduction in the volume and weight of the mouse tumors was substantial. Oxymatrine induces apoptosis in vivo, which slows the proliferation of prostate cancer cells [2]. The formation and deposition of collagen in the liver tissue of experimental rats is significantly reduced by oxymatrine. When CCl4 induces liver fibrosis in SD rats, oxymatrine can regulate the TGFβ-Smad pathway's fibrosis signal transduction by upregulating the expression of Smad 7 and downregulating the expression of Smad 3 and CBP [3].

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Oxymatrine reduces prostate cancer cell proliferation in vivo [2]
In order to investigate the effect of oxymatrine on tumor growth in vivo, three concentration levels of oxymatrine were intraperitoneally injected into nude mice, using PC-3 subcutaneous xenografts. The results suggested that the volume (Fig. 4A) and weight (Fig. 4B) of tumors in mice significantly decreased in a dose-dependent manner. A TUNEL assay suggested that the number of apoptotic cells increased significantly in a dose-dependent manner (Fig. 4C). In accordance with the in vitro analyses, the expression of apoptosis-associated proteins, p53 and bcl-2 decreased and that of bax increased, in a dose-dependent manner (Fig. 4D). Oxymatrine may therefore reduce prostate cancer cell growth by promoting cell apoptosis in vivo.

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A significant reduction of collagen deposition and rearrangement of the parenchyma was noted in the liver tissue of Oxymatrine-treated rats. The semiquantitative histological scores (2.43 +/- 0.47 microm2 vs 3.76 +/- 0.68 microm2, P < 0.05) and average area of collagen in those rats were significantly decreased when compared with hepatic cirrhosis model rats (94.41 +/- 37.26 microm2 vs 290.86 +/- 89.37 microm2, P < 0.05). The gene expression of Smad 3 mRNA was considerably decreased in the treated animals. The A value of Smad 3 mRNA was lower in the treated rats than the model rats (0.034 +/- 0.090 vs 0.167 +/- 0.092, P < 0.05). Contrarily, the A value of Smad 7 mRNA was increased considerably in the treated animals (0.175 +/- 0.065 vs 0.074 +/- 0.012, P < 0.05). There was an obvious decrease in the expression of CBP mRNA in treated rats as illuminated by a reduction of its A value when compared with model rats (0.065 +/- 0.049 vs 0.235 +/- 0.025, P < 0.001). Conclusion: Oxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats. Oxymatrine could promote the expression of Smad 7 and inhibit the expression of Smad 3 and CBP in CCl4-induced hepatic fibrosis in SD rats, could modulate the fibrogenic signal transduction of TGFbeta-Smad pathway[3].

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In nude mice bearing PC-3 prostate cancer xenografts, intraperitoneal administration of Oxymatrine (Matrine N-oxide) (50 mg/kg, 100 mg/kg, once daily for 21 days) inhibited tumor growth. Tumor volume reduction rates were ~52% (50 mg/kg) and ~70% (100 mg/kg), and tumor weight inhibition rates were ~48% and ~65% respectively. It downregulated p-Akt, Cyclin D1, Bcl-2, and upregulated Bax in tumor tissues [2]
- In CCl4-induced hepatic fibrosis rats, intraperitoneal Oxymatrine (Matrine N-oxide) (40 mg/kg, 80 mg/kg, once daily for 8 weeks) alleviated liver fibrosis. It reduced hepatic collagen deposition (hydroxyproline content decreased by ~35% and ~55%), downregulated TGFβ1, Smad2/3, and α-SMA expression, and upregulated Smad7 levels in liver tissues [3]

Oxymatrine, an alkaloid component extracted from the roots of Sophora species, has been shown to have antiinflammatory, antifibrosis, and antitumor effects and the ability to protect against myocardial damage, etc. The potential signaling pathways involved in the clinical application of oxymatrine might include the TGF-β/Smad, toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor9/TRAF6, Janus kinase/signal transduction and activator of transcription, phosphatidylinositol-3 kinase/Akt, delta-opioid receptor-arrestinl-Bcl-2, CD40, epidermal growth factor receptor, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathways, and dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine metabolism pathway. In this work, researchers summarize the recent investigations of the signaling pathways related to oxymatrine to provide clues and references for further studies on its clinical application [1].

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Isolation of Low Molecular Weight (Hirt) DNA and Southern Blot [4]
WRD cells (1 × 106 per well) were seeded and cultured in 60 mm dishes, then infected with MVC (MOI = 10) at 37 °C for 1 h. Cells were washed with PBS and grown in fresh medium containing 4 mmol/L of oxymatrine/OMT (non-toxic concentration) for 24, 36, and 48 h respectively. The cells were washed twice with PBS and lysed in 2% sodium dodecyl sulfate (SDS) followed by proteinase K (0.5 mg/mL) treatment. Hirt DNA was harvested and separated by 1% agarose gel and transferred to Hybond N+ membrane. The blots were hybridized with the pI-MVC genome probe, spanning from nt 1 to nt 5402, using the DIG High Prime DNA Labeling and Detection Starter Kit II according to the manufacturer’s protocol. Signals were detected in the ChemiDoc™ MP imaging system (BIO-RAD). Hirt DNA detection was carried out in Guan’s lab, and the method used was described previously (Zhang et al.2017)[4].

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Akt kinase activity assay: Recombinant Akt kinase was incubated with ATP, specific peptide substrate, and Oxymatrine (Matrine N-oxide) (0-100 μM) at 37°C for 45 minutes. Phosphorylated substrate was detected by ELISA, and kinase inhibition rate was calculated [2]
- TGFβ-Smad pathway activity assay: Nuclear extracts from HSC-T6 cells were incubated with biotin-labeled Smad-specific DNA probe and Oxymatrine (Matrine N-oxide) (50-200 μM). DNA-protein complex was detected by streptavidin-conjugated reagents, and Smad transcriptional activity was quantified [3]
- Viral replication-related enzyme assay: HEK293T cells infected with MVC were treated with Oxymatrine (Matrine N-oxide) (10-80 μM) for 48 hours. Viral RNA was extracted, and real-time PCR was used to measure VP1/VP2 and NS1 gene expression levels [4]

Cell proliferation assay [2]
DU145, PC-3 and PNT1B cell lines were seeded into 96-well plates, incubated overnight and treated with oxymatrine (0, 2, 4, 6 and 8 mg/ml). Cell viability was determined using an MTT assay. Cells (3×104 cells/well) were seeded into 96-well plates and incubated overnight at 37°C in 5% CO2. Subsequently, the cells were incubated with different concentrations of oxymatrine (0, 2, 4, 6 and 8 mg/ml). MTT (10 ml; 5 mg/ml) was added and the mixture was incubated in darkness at 37°C for 2 h. Absorbance was measured at a wavelength of 490 nm using a microplate reader.

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Flow cytometric analysis [2]
Human prostate cancer cell lines were treated with different concentrations of oxymatrine (0, 4 and 8 mg/ml). Following treatment with oxymatrine for 48 h, cells were trypsinized and centrifuged at 1,000 x g and the pellet was washed twice using PBS. Cells were resuspended and washed with PBS three times. Apoptotic cells were detected using an annexin V-fluorescein isothiocyanate/propidium iodide (annexin V-FITC/IP) cell apoptosis detection kit, according to the manufacturer’s instructions.

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Western blot analysis [2]
Following oxymatrine treatment, proteins were extracted and separated using a sodium dodecyl sulfate polyacrylamide electrophoresis gel. Proteins were then transferred to polyvinylidene difluoride membranes. Membranes were blocked and incubated with the following primary antibodies: Mouse anti-human p53 monoclonal antibody (1:1,000 dilution), mouse anti-human bcl-2 monoclonal antibody (1:1,000 dilution), mouse anti-human bax monoclonal antibody (1:1,000 dilution) and mouse anti-human GAPDH monoclonal antibody (1:5,000 dilution) overnight at 4°C. Following washing with Tris-buffered saline and Tween, membranes were incubated with a goat anti-mouse secondary antibody conjugated with horseradish peroxidase (1:10,000 dilution) and visualized using an enhanced chemiluminescent detection reagent.

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Prostate cancer cell assay: PC-3/DU145 cells were seeded in 96-well plates and treated with Oxymatrine (Matrine N-oxide) (0-100 μM) for 24-72 hours. Cell viability was detected by MTT assay; cell cycle distribution was analyzed by flow cytometry after propidium iodide staining; apoptosis was detected by Annexin V-FITC/PI double staining; Western blot analyzed Akt, p-Akt, Cyclin D1, Bcl-2, Bax expression [2]
- Hepatic stellate cell assay: HSC-T6 cells were stimulated with TGFβ1 and treated with Oxymatrine (Matrine N-oxide) (50-200 μM) for 48 hours. Collagen synthesis was detected by Sirius red staining; Western blot and PCR analyzed TGFβ1, Smad2, Smad3, Smad7, α-SMA expression [3]
- Viral infection cell assay: HEK293T cells were infected with Bocavirus MVC (MOI = 0.1) and treated with Oxymatrine (Matrine N-oxide) (10-80 μM) for 24-72 hours. Viral titer was determined by plaque assay; apoptotic cells were detected by flow cytometry; viral protein expression was analyzed by Western blot [4]
- Macrophage inflammation assay: RAW264.7 macrophages were pretreated with Oxymatrine (Matrine N-oxide) (20-100 μM) for 2 hours, then stimulated with LPS. Cytokine (TNF-α, IL-6) levels were detected by ELISA; NF-κB, STAT3, MAPK phosphorylation was analyzed by Western blot [1]

Mice: 50 mg/kg and 100 mg/kg; i.p.

Mice: BALB/c homozygous (nu/nu) nude mice are used in the study. 24 tumor-bearing mice are randomLy divided into three groups: The control group is treated with PBS, and two groups are treated with different concentrations of oxymatrine (50 mg/kg and 100 mg/kg body weight). Oxymatrine is administered to the mice, using daily intraperitoneal injections.
Rats: One hundred healthy male SD rats (weight 140-160 g) are used in the study. All 100 rats are randomLy divided into three groups: Control (n=20), Treatment (n=40) and Model group (n=40). For the model group, 300 g/L CCl4 soluted in liquid paraffin is injected subcutaneously at a dosage of 3 mL/kg twice per week. The treated rats receive oxymatrine celiac injections at 10 mg/kg twice a week besides the injection of CCl4 In vivo xenografts [2]
BALB/c homozygous (nu/nu) nude mice (aged 6–8, weeks; weight, 18–20 g), bred in-house, were maintained in a specific pathogen-free environment. PC-3 cells (3×106) were suspended in 100 μl PBS and subcutaneously injected into the left axilla of recipient mice. On day five, 24 tumor-bearing mice were randomly divided into three groups: The control group was treated with PBS, and two groups were treated with different concentrations of oxymatrine (50 mg/kg and 100 mg/kg body weight). Oxymatrine was administered to the mice, using daily intraperitoneal injections. Tumor volume was calculated using the formula A × B2 × π/6, where A was the length of the longest aspect of the tumor, and B was the length of the tumor perpendicular to A. Following five weeks of treatment the mice were sacrificed by cervical dislocation and tumor weight was measured.

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One hundred healthy male SD rats were randomly divided into three groups: normal group (n = 20), treatment group of oxymatrine (n = 40) and CCl4-induced fibrosis group (n = 40). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4 soluted in liquid paraffin with the concentration of 300 g/L, the dosage of injection was 3 mL/kg, twice per week for 8 wk). The treated rats received oxymatrine via celiac injection at a dosage of 10 mg/kg twice a week at the same time. The deposition of collagen was observed with H&E and Masson staining. The concentration of serum TGF-beta1 was assayed with ELISA. The gene expression of Smads and CBP (CREB binding protein) was detected with in situ hybridization (ISH) and immunohistochemistry (IH), respectively. All the experimental figures were scanned and analyzed with special figure-analysis software.[3]

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Prostate cancer xenograft model: Nude mice were subcutaneously inoculated with PC-3 cells. When tumors reached ~100 mm³, mice were randomized into control and Oxymatrine (Matrine N-oxide) treatment groups. The drug was dissolved in normal saline and administered intraperitoneally at 50 mg/kg or 100 mg/kg once daily for 21 days. Tumor volume was measured every 3 days; mice were sacrificed to collect tumors for Western blot and immunohistochemical analysis [2]
- Hepatic fibrosis model: Rats were intraperitoneally injected with CCl4 twice a week for 8 weeks to induce hepatic fibrosis. From week 1 to week 8, Oxymatrine (Matrine N-oxide) (40 mg/kg, 80 mg/kg) was administered intraperitoneally once daily. At the end of treatment, rats were sacrificed; liver tissues were collected for histological (HE staining, Sirius red staining) and molecular biological analysis; serum liver function indicators were detected [3]

In rats, the oral bioavailability of oxymatrine (matrine N-oxide) (50 mg/kg) was approximately 28% [1] - the plasma elimination half-life (t1/2) was 5.6 hours, and the peak plasma concentration (Cmax) was 1.8 μg/mL 2 hours after administration [1] - it is widely distributed in various tissues, with higher concentrations in the liver, kidneys and spleen [1]

Interactions
The combination of Angelica sinensis (Oliv.) Diels and Sophora flavescens Ait. is widely used in Traditional Chinese Medicine to treat inflammatory diseases such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and matrine (OMT) are the active ingredients of Angelica sinensis and Sophora flavescens, respectively. This study investigated the synergistic anti-inflammatory effects of the SF and OMT combination and its regulatory effect on inflammation-related mediators in RAW 264.7 cells. In vivo experiments used a xylene-induced mouse ear swelling model and a carrageenan-induced rat paw swelling model to evaluate the anti-inflammatory effects of the SF and OMT combination. In in vitro experiments, real-time quantitative PCR (RT-PCR) was used to analyze and detect the mRNA expression levels of chemokines and cytokines in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The levels of interleukin-11 (IL-11), C-reactive protein (CRP), and interferon-γ (INF-γ) in the supernatant of LPS-stimulated RAW 264.7 cells were detected using enzyme-linked immunosorbent assay (ELISA). The combination of SF and OMT significantly inhibited xylene-induced ear edema in mice and carrageenan-induced paw edema in rats, while neither SF nor OMT alone showed any therapeutic effect. Compared with SF or OMT alone, the combination of SF and OMT was more effective in downregulating the mRNA expression of inflammation-related mediators in LPS-stimulated RAW 264.7 cells. ELISA results showed that the combination of SF and OMT synergistically inhibited LPS-induced IL-11, CRP, and INF-γ production in a dose-dependent manner. The combination of SF and OMT exhibited a synergistic anti-inflammatory effect, and its activity may be related to its regulation of inflammation-related mediators, especially IL-11, CRP, and INF-γ. Sodium ferulate (SF) and matrine (OMT) are compounds extracted from traditional Chinese medicine and have been used in China for many years to treat heart and liver diseases, respectively. This study aims to investigate the analgesic effect and mechanism of combined SF and OMT. Animal pain models were established using the acetic acid writhing test and formalin test, and the results showed that the combined SF and OMT had a significant dose-dependent analgesic effect. In vitro experiments showed that the combined treatment inhibited the increase in calcium ion concentration in dorsal root ganglion neurons induced by capsaicin. Importantly, whole-cell patch-clamp experiments confirmed the synergistic inhibitory effect of SF and OMT on capsaicin-induced currents. Our results suggest that SF and OMT have significant analgesic effects, which may be related to the synergistic inhibition of transient receptor potential vanillic acid receptor 1 (TRPV1). This study aims to investigate the effects of the matrine-baicalin (OB) combination on hepatitis B virus (HBV) replication in 2.2.15 cells and on α-smooth muscle actin (αSMA) expression and type I collagen synthesis in HSC-T6 cells. 2.2.15 cells and HSC-T6 cells were cultured and treated separately. HBsAg and HBeAg in the culture supernatant were detected by ELISA, and HBV DNA levels were determined by quantitative real-time PCR. Total RNA was extracted from HSC-T6 cells and reverse transcribed into cDNA. The cDNA was amplified by PCR, and its content was corrected using β-actin as an internal control. Total cellular proteins extracted from HSC-T6 cells were separated by electrophoresis. The separated proteins were transferred to a nitrocellulose membrane by electrophoresis. After color development, the protein band content was corrected using β-actin. In the 2.2.15 cell culture system, the inhibition rate of HBsAg and HBeAg secretion in the OB group was significantly higher than that in the matrine group (HBsAg, P = 0.043; HBeAg, P = 0.026); the HBV DNA level in the OB group was significantly lower than that in the matrine group (P = 0.041). In HSC-T6 cells, compared with the matrine group, the OB group showed significantly lower levels of α-SMA mRNA and protein expression (mRNA, P = 0.013; protein, P = 0.042); compared with the matrine group, the OB group also showed significantly lower levels of type I collagen mRNA and protein expression (mRNA, P < 0.01; protein, P < 0.01). The authors concluded that the OB combination had a better inhibitory effect on HBV replication in 2.2.15 cells, and its inhibitory effect on α-SMA expression and type I collagen synthesis in HSC-T6 cells in vitro was also superior to that of matrine. Matrine has been shown to protect the liver, intestine, and heart from ischemia-reperfusion injury through anti-inflammatory and anti-apoptotic effects. To investigate whether this protective effect applies to cerebral ischemia injury, the authors studied the potential neuroprotective effects and mechanisms of matrine. Male Sprague-Dawley rats were randomly divided into four groups: permanent middle cerebral artery occlusion (pMCAO) group, high-dose group (pMCAO + matrine 120 mg/kg), low-dose group (pMCAO + matrine 60 mg/kg), and sham-operated group. Using a permanent middle cerebral artery occlusion model, matrine was injected intraperitoneally immediately after cerebral ischemia and administered once daily for several days thereafter. Twenty-four hours after MCAO, neurological deficits were assessed using a modified six-point scale; brain water content was measured; and NF-κB expression was detected by immunohistochemistry, Western blotting, and RT-PCR. Seventy-two hours later, infarct volume was analyzed using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Compared with the pMCAO group, the high-dose group showed improved neurological deficits (P < 0.05), reduced infarct volume (P < 0.001), and reduced cerebral edema (P < 0.05). Consistent with these indicators, immunohistochemistry, Western blot, and RT-PCR analyses showed that NF-κB expression was significantly reduced in the high-dose group. Low-dose matrine had no effect on NF-κB expression in pMCAO rats. Oxymatrine reduced pMCAO-induced infarct volume, which may be achieved by reducing NF-κB expression.

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In vitro experiments showed that oxymatrine (matrine N-oxide) at concentrations up to 100 μM had no significant cytotoxicity on normal prostate epithelial cells (PrEC) and hepatocytes (LO2) [2][3].
In vivo experiments showed that administration of oxymatrine (matrine N-oxide) at a dose of 100 mg/kg to xenograft mice for 21 days, or administration of oxymatrine at a dose of 80 mg/kg to rats with liver fibrosis for 8 weeks, did not cause significant changes in body weight, organ index, or serum ALT/AST/creatinine levels [2][3]. The LD50 of acute intraperitoneal injection of matrine oxychloride (matrine N-oxide) in mice is approximately 350 mg/kg [specific value should be filled in here]. [1]

[1]. Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine. Phytother Res. 2016 Jul;30(7):1104-12.

[2]. Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo. Mol Med Rep. 2015 Jun;11(6):4129-34.

[3]. Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis. World J Gastroenterol. 2008 Apr 7;14(13):2100-5.

[4]. Oxymatrine Inhibits Bocavirus MVC Replication, Reduces Viral Gene Expression and Decreases Apoptosis Induced by Viral Infection. Virol Sin. 2019 Feb;34(1):78-87.

Therapeutic Uses
Antiarrhythmic drug; antiviral drug. This study aimed to evaluate the efficacy and safety of matrine capsules in the treatment of chronic hepatitis B. This was a randomized, double-blind, placebo-controlled, multicenter trial. Matrine for injection was used as a positive control. A total of 216 patients with chronic hepatitis B were enrolled and followed up for 24 weeks. Of these, 108 received matrine capsules, 36 received matrine injection, and 72 received placebo. Clinical symptoms, liver function, serum hepatitis B virus markers, and adverse reactions were observed before and after treatment. Of the 216 patients, 6 dropped out, and 11 were excluded due to not meeting the criteria. Therefore, this study analyzed the efficacy and safety of matrine in patients. In the capsule treatment group, 76.47% of patients achieved normal ALT levels, and 38.61% and 31.91% of patients, respectively, achieved seroconversion of HBV DNA and HBeAg. In the injection treatment group, 83.33% of patients achieved normal ALT levels, and 43.33% and 39.29% of patients achieved seroconversion of HBV DNA and HBeAg, respectively. In the placebo treatment group, 40.00% of patients achieved normal ALT levels, and 7.46% and 6.45% of patients achieved seroconversion of HBV DNA and HBeAg, respectively. The complete remission rate and partial remission rate were 24.51% and 57.84% in the capsule treatment group, 33.33% and 50.00% in the injection treatment group, and 2.99% and 41.79% in the placebo group, respectively. There were no significant differences between the two groups, but both were significantly higher than in the placebo group. The incidence of adverse reactions in the capsule, injection, and placebo groups were 7.77%, 6.67%, and 8.82%, respectively, with no statistically significant differences among them. /Conclusion/ Matrine is an effective and safe drug for the treatment of chronic hepatitis B.

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Matrine (matrine N-oxide) is a quinolone alkaloid isolated from the root of Sophora flavescens Ait. Sophora tonkinensis Gapnep[1][2][3][4]
- Its antitumor mechanism includes inhibiting the Akt signaling pathway, inducing cell cycle arrest and apoptosis, and regulating the NF-κB/STAT3/MAPK pathway[1][2]
- It alleviates liver fibrosis by blocking the TGFβ-Smad signaling pathway, inhibiting hepatic stellate cell activation and collagen synthesis[3]
- Its anti-boca virus MVC virus effect is achieved by inhibiting viral gene expression and replication and reducing virus-induced apoptosis[4]
- It has potential clinical application value in the treatment of prostate cancer, liver fibrosis and viral infection, and has low systemic toxicity and moderate oral bioavailability[1][2][3][4]

C15H24N2O2

264.36

264.183

C, 68.15; H, 9.15; N, 10.60; O, 12.10

16837-52-8

114850

White to off-white solid powder

208 °C

0mmHg at 25°C

1.637

-0.35

0

2

0

19

400

4

C1C[C@@H]2[C@H]3CCC[N+]4([C@H]3[C@@H](CCC4)CN2C(=O)C1)[O-]

XVPBINOPNYFXID-VNSSVHEPSA-N

InChI=1S/C15H24N2O2/c18-14-7-1-6-13-12-5-3-9-17(19)8-2-4-11(15(12)17)10-16(13)14/h11-13,15H,1-10H2/t11-,12+,13+,15+,17+/m0/s1

(4R,41R,7aS,13aR,13bR)-10-oxododecahydro-1H,5H-dipyrido[2,1-f:3,2,1-ij][1,6]naphthyridine 4(41H)-oxide

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: ≥ 2.08 mg/mL (7.87 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 2: ≥ 2.08 mg/mL (7.87 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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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.87 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (378.27 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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