Category Archives: Paeonia suffruticosa

ameliorated myelosuppression, anti-apoptotic, apoptosis, Apoptotic, BAX, Bcl-2, Bcl-xL, c-Jun, Chapter 7 Isolates and Cancer Research, chemo-preventive, Chemo-preventive agent, Chemotherapy, Colon Cancer or Colorectal cancer, EP2, EP4, ERK, Gastric cancer or Stomach cancer, HepG2, SMMC-7721, HT29, JNK, Liver cancer, MDR, Multi-Drug Resistance, Multi-drug resistance, p38, Paeonia suffruticosa, PCNA, PGE2, Radio-protective, radio-protective effect, Rectal cancer, ROS, SGC7901/VCR

Paeoniflorin

Cancer: Hepatocellular carcinoma, colorectal, liver

Action: Radio-protective, ameliorated myelosuppression, MDR

Radio-protective

The radio-protective effect of paeoniflorin (PF), a main bioactive component in the traditional Chinese herb peony, on irradiated thymocytes and the possible mechanisms of protection have been investigated. Ionizing radiation can induce DNA damage and cell death by generating reactive oxygen species (ROS).

It was found 60Co γ-ray irradiation increased cell death and DNA fragmentation in a dose-dependent manner while increasing intracellular ROS. Pre-treatment of thymocytes with PF (50–200 µg/ml) reversed this tendency and attenuated irradiation-induced ROS generation. Hydroxyl-scavenging action of PF in vitro was detected through electron spin resonance assay. Several anti-apoptotic characteristics of PF, including the ability to diminish cytosolic Ca2+ concentration, inhibit caspase-3 activation, and up-regulate Bcl-2 and down-regulate Bax in 4 Gy-irradiated thymocytes, were determined.

Extracellular regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 kinase, were activated by 4 Gy irradiation, with their activation partly blocked by pre-treatment of cells with PF. The presence of ERK inhibitor PD98059, JNK inhibitor SP600125 and p38 inhibitor SB203580 decreased cell death in 4 Gy-irradiated thymocytes. These results suggest PF protects thymocytes against irradiation-induced cell damage by scavenging ROS and attenuating the activation of the mitogen-activated protein kinases (Li et al., 2007).

Liver Cancer

Prostaglandin E2 (PGE2) has been shown to play an important role in tumor development and progression. PGE2 mediates its biological activity by binding any one of four prostanoid receptors (EP1 through EP4). Paeoniflorin, a monoterpene glycoside, significantly inhibited the proliferation of HepG2 and SMMC-7721 cells stimulated by butaprost at multiple time points (24, 48, and 72 hours). Paeoniflorin induced apoptosis in HepG2 and SMMC-7721 cells, which was quantified by annexin-V and propidium iodide staining. Our results indicate that the expression of the EP2 receptor and Bcl-2 was significantly increased, whereas that of Bax and cleaved caspase-3 was decreased in HepG2 and SMMC-7721 cells.

Paeoniflorin, which may be a promising agent in the treatment of liver cancer, induced apoptosis in hepatocellular carcinoma cells by down-regulating EP2 expression and also increased the Bax-to-Bcl-2 ratio, thus up-regulating the activation of caspase-3 (Hu et al., 2013).

Colorectal Cancer

Results showed that positive cells of Proliferating Cell Nuclear Antigen (PCNA) in paeoniflorin (PF) and docetaxel-treated group was decreased to 30% and 15% respectively, compared with control group of tumors. But apoptosis cells in docetaxel treated groups studied by TUNEL is increased to 40 ± 1.2% and 30 ± 1.5% respectively, compared with 24 ± 2.3% in negative control. Furthermore, the efficiency of tumor-bearing mice treated by PF was superior to docetaxel in vivo. Overall, PF may be an effective chemo-preventive agent against colorectal cancer HT29 (Wang et al., 2012).

Ameliorates Myelosuppression

The administration of paeoniflorin and albiflorin (CPA) extracted from Paeonia radix, significantly ameliorated myelosuppression in all cases. For the X-ray irradiated mice and the chemotherapy treated mice and rabbits, high dosages of CPA resulted in the recovery of, respectively, 94.4%, 95.3% and 97.7% of hemoglobin content; 67.7%, 92.0% and 94.3% of platelet numbers; 26.8%, 137.1% and 107.3% of white blood cell counts; as well as a reversal in the reduction of peripheral differential white blood cell counts.

There was also a recovery of 50.9%, 146.1% and 92.3%, respectively, in the animals' relative spleen weight. Additionally, a recovery of 35.7% and 87.2% respectively in the number of bone marrow nucleated cells was observed in the radio- and chemo -therapy-treated mice. Bone marrow white blood cell counts also resumed to normal levels (Xu et al., 2011).

MDR

Studies have shown that NF-κB activation may play an essential role in the development of chemotherapy resistance in carcinoma cells. Paeonißorin, a principal bioactive component of the root of Paeonia lactißora, has been reported to exhibit various pharmacological effects. In the present study, Fanh et al. (2012) reported for the first time that paeoniflorin at non-toxic concentrations may effectively modulate multi-drug resistance (MDR) of the human gastric cancer cell line SGC7901/vincristine (VCR) via the inhibition of NF-κB activation and, at least partly, by subsequently down-regulating its target genes MDR1, BCL-XL and BCL-2.

References

Fang S, Zhu W, Zhang Y, Shu Y, Liu P. (2012). Paeoniflorin modulates Multi-drug resistance of a human gastric cancer cell line via the inhibition of NF- κB activation. Mol Med Rep, 5(2):351-6. doi: 10.3892/mmr.2011.652.


Hu S, Sun W, Wei W, et al. (2013). Involvement of the prostaglandin E receptor EP2 in paeoniflorin-induced human hepatoma cell apoptosis. Anti-cancer Drugs, 24(2):140-9. doi: 10.1097/CAD.0b013e32835a4dac.


Li CR, Zhou Z, Zhu D, et al. (2007). Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. The International Journal of Biochemistry & Cell Biology, 39(2):426–438


Wang H, Zhou H, Wang CX, et al. (2012). Paeoniflorin inhibits growth of human colorectal carcinoma HT 29 cells in vitro and in vivo. Food Chem Toxicol, 50(5):1560-7. doi: 10.1016/j.fct.2012.01.035.


Xu W, Zhou L, Ma X, et al. (2011). Therapeutic effects of combination of paeoniflorin and albiflorin from Paeonia radix on radiation and chemotherapy-induced myelosuppression in mice and rabbits. Asian Pac J Cancer Prev, 12(8):2031-7.

anti-inflammatory, anti-oxidant, anxiolytic, apoptosis, apoptosis-inducing, Apoptotic, BAX, Bcl-2, Chapter 7 Isolates and Cancer Research, COX-2, COX-2 down-regulation, FasL, G0/G1, G1, Gastric cancer or Stomach cancer, growth-inhibitory, HT-29, IL-1, IL-6, induces apoptosis, inflammation, Nitric Oxide, p27, Paeonia suffruticosa, S, TNF

Paenol

Cancer: Gastric

Action: Attenuates nephrotoxicity, anti-inflammatory, anti-oxidant, inhibits TNF- α , induces apoptosis, COX-2 down-regulation

Inhibits TNF- α

Moutan Cortex, the root bark of Paeonia suffruticosa Andrews, has been used extensively as a traditional medicine for treatment of various diseases such as atherosclerosis, infection, and inflammation. Previous studies have revealed that the extracts of Moutan Cortex can inhibit nitric oxide and TNF- α in activated mouse peritoneal macrophages (Chung et al., 2007).

A variety of compounds including paeonoside, paeonolide, apiopaeonoside, paeoniflorin, oxypaeoniflorin, benzoyloxypaeoniflorin, benzoylpaeoniflorin, paeonol, and sugars have been identified in Moutan Cortex (Chen et al., 2006).

Attenuates Nephrotoxicity

Paeonol, a major compound of Moutan Cortex, has been found to attenuate cisplatin-induced nephrotoxicity in mice. Cisplatin is an effective chemotherapeutic agent that is used for the treatment of a variety of cancers; however, its nephrotoxicity limits the use of this drug.

Balb/c mice (6 to 8  w of age, weighing 20 to 25  g) were administered with Moutan Cortex (300  mg/kg) or paeonol (20 mg/kg) once a day. At day 4, mice received cisplatin (30, 20, or 10   mg/kg) intraperitoneally.

The paeonol-treated group showed marked attenuation of serum creatine and blood urea nitrogen levels as well as reduced levels of pro-inflammatory cytokines and nitric oxide when compared to the control group. In addition, the paeonol-treated group showed prolonged survival and marked attenuation of renal tissue injury. Taken together, these results demonstrated that paeonol can prevent the renal toxic effects of cisplatin (Lee et al., 2013).

Paeonol, a major phenolic component of Moutan Cortex, has various biological activities such as anti-aggregatory, anti-oxidant, anxiolytic-like, and anti-inflammatory functions (Ishiguro et al., 2006). In this study, paeonol treatment significantly reduced the elevated levels of serum creatinine and BUN. In addition, the role of pro-inflammatory cytokines in cisplatin-induced acute renal failure has been well documented (Faubel et al., 2007; Ramesh & Reeves, 2002), and elevation of the pro-inflammatory cytokines TNF-α and IL-1β as well as that of IL-6 has been demonstrated in humans with acute renal failure (Simmons et al., 2004).

Apoptosis-inducing & Gastric Cancer

Paeonol has significantly growth-inhibitory and apoptosis-inducing effects in gastric cancer cells both in vitro and in vivo. In vitro, paeonol caused dose-dependent inhibition on cell proliferation and induced apoptosis. Cell cycle analysis revealed a decreased proportion of cells in G0/G1 phase, with arrest at S. Paeonol treatment in gastric cancer cell line MFC and SGC-790 cells significantly reduced the expression of Bcl-2 and increased the expression of Bax in a concentration-related manner. Administration of paeonol to MFC tumor-bearing mice significantly lowered the tumor growth and caused tumor regression (Li et al., 2010).

COX-2 Down-regulation

One of the apoptotic mechanisms of paeonol is down-regulation of COX-2. p27 is up-regulated simultaneously and plays an important part in controlling cell proliferation and is a crucial factor in the Fas/FasL apoptosis pathway. Cell proliferation was inhibited by different concentrations of paeonol. By immunocytochemical staining, Ye et al. (2009) found that HT-29 cells treated with paeonol (0.024-1.504 mmol/L) reflected reduced expression of COX-2 and increased expression of p27 in a dose-dependent manner. RT-PCR showed that paeonol down-regulated COX-2 and up-regulated p27 in a dose- and time-dependent manner in HT-29 cells.

References

Chen G, Zhang L, Zhu Y. (2006). Determination of glycosides and sugars in moutan cortex by capillary electrophoresis with electrochemical detection. Journal of Pharmaceutical and Biomedical Analysis, 41(1):129–134.


Chung HS, M. Kang, C. Cho et al. (2007). Inhibition of nitric oxide and tumor necrosis factor-alpha by moutan cortex in activated mouse peritoneal macrophages. Biological and Pharmaceutical Bulletin, 30(5):912–916.


Faubel F, Lewis EC, Reznikov L et al. (2007). Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1 β , IL-18, IL-6, and neutrophil infiltration in the kidney. Journal of Pharmacology and Experimental Therapeutics, 322(1):8–15.


Ishiguro K, Ando T, Maeda O et al. (2006). Paeonol attenuates TNBS-induced colitis by inhibiting NF- κ B and STAT1 transactivation. Toxicology and Applied Pharmacology, 217(1):35–42.


Lee HJ, Lee GY, Kim Hs, Bae Hs. (2013). Paeonol, a Major Compound of Moutan Cortex, Attenuates Cisplatin-Induced Nephrotoxicity in Mice. Evidence-Based Complementary and Alternative Medicine, 2013(2013), http://dx.doi.org/10.1155/2013/310989


Li N, Fan LL, Sun GP, et al. (2010). Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo. World J Gastroenterol., 16(35):4483-90.


Ramesh G, Reeves wb. (2002). TNF- α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. Journal of Clinical Investigation, 110(6):835–842.


Simmons EM, Himmelfarb j, Sezer MT et al. (2004). Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney International, 65(4):1357–1365.


Ye JM, Deng T, Zhang JB. (2009) Influence of paeonol on expression of COX-2 and p27 in HT-29 cells. World J Gastroenterol, 15(35):4410-4.