Anti-inflammatory activity and chemical composition of dichloromethane extract from Piper nigrum and P. longum on permanent focal cerebral ischemia injury in rats

Abstract

White pepper (Piper nigrum L.) and long pepper (Piper longum L.) belong to family Piperaceae and are commonly used as household spices and traditional medicine worldwide, specifically in China and Southeast Asia. In Traditional Chinese Hui Medicine, these herbs are widely used for treatment of stroke. Our present study investigated effects of these herbs on inflammation in rat model with cerebral ischemia. After subjecting the rats to permanent middle cerebral artery occlusion (pMCAO) for 6 h, at doses of 100 and 200 mg/kg, dichloromethane fraction from white pepper and long pepper, respectively, was intragastrically administered once a day for seven consecutive days. Cerebral cortical and hippocampal tissues were collected after seven days. Superoxide dismutase, malonaldehyde, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were measured by spectrophotometer. Phytochemical profile of dichloromethane fraction was determined through HPLC. Dichloromethane fraction exhibited anti-inflammatory activity by suppressing expression or production of IL-1β, IL-6, and TNF-α. By contrast, dichloromethane fraction showed activity against pMCAO injury by reducing oxygen-free radicals through increased superoxide dismutase activity and decreased malonaldehyde level. HPLC analysis revealed piperine as major component of dichloromethane fraction. These results show that dichloromethane fraction provides protection against cerebral ischemia. The possible mechanism is related to anti-inflammatory activity and reduction in oxygen-free radicals.

References

  1. Ahmed, M.A.E., Morsy, E.I.E.M., Ahmed, A.A.E., 2014. Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats. Life Sci. 110, 61–69.

    CAS  Article  PubMed  Google Scholar 

  2. Banji, D., Banji, O.J., Dasaroju, S., Kranthi, K.C., 2013. Curcumin and piperine abrogate lipid and protein oxidation induced by D-galactose in rat brain. Brain Res. 1515, 1–11.

    CAS  Article  PubMed  Google Scholar 

  3. Chang, C.Y., Kuan, Y.H., Li, J.R., Chen, W.Y., Ou, Y.C., Pan, H.C., Liao, S.L., Raung, S.L., Chang, C.J., Chen, C.J., 2013. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. J. Nut. Biochem. 24, 2127–2137.

    CAS  Article  Google Scholar 

  4. Commission, C.P., 2015. China Pharmacopoeia, vol. I. China Medical Science Press, Beijing.

  5. Daniela, E.E.C.D., Evelyn, A.J., Martin, S., Maxime, C., Fabien, G., Romeo, C., Hans, C.C.H., Birger, B., Laurin, W., Marko, D.M., Matthias, H., Mouhssin, O., 2016. In vitro blood-brain barrier permeability predictions for gabaa receptor modulating piperine analogs. Eur. J. Pharm. Biopharm. 103, 118–126.

    Article  Google Scholar 

  6. Hao, W.J.L., Ge, G., Xia, W., Xiao, W., Hui, Y., 2016. Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury. Brain Res. 1636, 214–227.

    Google Scholar 

  7. Hu, D., Wang, Y., Chen, Z., Ma, Z., You, Q., Zhang, X., 2015. The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation. J. Ethnopharmacol. 169, 109–123.

    CAS  Article  PubMed  Google Scholar 

  8. Ishrat, T., Sayeed, I., Atif, F., Hua, F., Stein, D.G., 2010. Progesterone and allopreg-nanolone attenuate blood-brain barrier dysfunction following permanent focal ischemiaby regulating the expression of matrix metalloproteinases. Exp. Neurol. 226, 183–190.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Kao, T.K., Chang, C.Y., Ou, Y.C., Chen, W.Y., Kuan, Y.H., Pan, H.C., 2013. Tetram-ethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. Exp. Neurol. 247, 188–201.

    CAS  Article  PubMed  Google Scholar 

  10. Kim, H.G., Eun, H.H., Woo, S.J., Jae, H.C., Tilak, K., Bong, H.P., 2012. Piperine inhibits PMA-induced cyclooxygenase-2 expression through downregulating NF-KB, C/EBP and Ap-1 signaling pathways in murine macrophages. Food Chem. Toxicol. 50, 2342–2348.

    CAS  Article  PubMed  Google Scholar 

  11. Kogure, H.N.A.K., 1989. Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20, 1037–1043.

    Article  PubMed  Google Scholar 

  12. Koizumi, J.I., Oshid, Y.Y., Nakazawa, T., Ooneda, G., 1986. Experimental studies of ischemic brain edema, a new experimental model of cerebral embolism in rats in which recirculation can be introduced. Stroke 8, 1–8.

    Google Scholar 

  13. Li, J., Dong, Y., Chen, H., Han, H., Yu, Y., Wang, G., 2012. Protective effects of hydrogen-rich saline in a rat model of permanent focal cerebral ischemia via reducing oxidative stress and inflammatory cytokines. Brain Res 1486, 103–111.

    CAS  Article  PubMed  Google Scholar 

  14. Li, J., Yang, L., Hui, L., Fei, R., Xic, H., 2014. Effects of Zhali Nusi Fang on permeability changes of blood brain barrier after focal cerebral ischemia-reperfusion in rats. Chin. J. Exp. Trad. Med. Formul. 20, 114–117 (in Chinese).

    Google Scholar 

  15. Li, T.T., Lin, D., Chen, G.T., Chen, J., Fu, X.Y., 2013a. Summary of Hui prescriptions for stroke. China J. Chin. Mater. Med. 38, 2412–2415 (in Chinese).

    Google Scholar 

  16. Li, T.T., Wang, X., Ma, X.Q., Chen, J., Fu, X.F., 2013b. Prescriptions compatibility law research for stroke treatment in Hui medicine. Chin. J. Exp. Trad. Med. Formul. 19, 307–311 (in Chinese).

    CAS  Google Scholar 

  17. Liu, J.X., Li, J.S., Niu, Y., Yu, W., Hei, C.C., Liu, H., 2011. Neuroprotective effect of Zhali Nusi and Mijian Changpu recipes against cerebral ischemia injury in rats. J. Ningxia Med. Univ. 33, 1001–1103 (in Chinese).

    Google Scholar 

  18. Luo, Y., Yang, Y.P., Liu, J., Li, W.H., Yang, J., Sui, X., 2014. Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats. Brain Res. 1565, 37–47.

    CAS  Article  PubMed  Google Scholar 

  19. Qing, Q.M.Z.H., Zhong, X.M., Yan, F.X., Siu, P.I., 2014. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice. Behav. Brain Res. 261, 140–145.

    Article  Google Scholar 

  20. Samra, Y.A.H.S.S., Nehal, M.E., Gregory, I.L., Mamdouh, M.E., Laila, A.E., 2016. Cepha-ranthine and piperine ameliorate diabetic nephropathy in rats, role of NF-KB and NLRP3 inflammasome. Life Sci. 157, 189–199.

    Article  Google Scholar 

  21. Scott, W.P.K., Anna, L.G., Mat, N., David, W.H., Karen, B., 2016. Resveratrol, piperine and apigenin differ in their NADPH-oxidase inhibitory and reactive oxygen species-scavenging properties. Phytomedicine 23, 1494–1503.

    Article  Google Scholar 

  22. Shu, Y., Yang, Y., Zhang, P., 2016. Neuroprotective effects of phenylcyclidine hydrochloride against cerebral ischemia/reperfusion injury in mice. Brain Res. Bull. 121, 115–123.

    CAS  Article  PubMed  Google Scholar 

  23. Singh, D.P., Chopra, K., 2013. Verapamil augments the neuroprotectant action of berberine in rat model of transient global cerebral ischemia. Eur. J. Pharmacology. 720, 98–106.

    CAS  Article  Google Scholar 

  24. Singh, P., Singh, I.N., Mondal, S.C., Singh, L., Garg, V.K., 2013. Platelet-activating factor (Paf)-antagonists of natural origin. Fitoterapia 84, 180–201.

    CAS  Article  PubMed  Google Scholar 

  25. Son, D.J., Soo, Y.K., Seong, S.H., Chan, W.K., Sandeep, K., Byeoung, S.P., 2012. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling. Biochem. Biophys. Res. Co. 427, 349–354.

    CAS  Article  Google Scholar 

  26. Tao, X., Sun, X., Yin, L., Han, X., Xu, L., Qj, Y., 2015. Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition. Free Radical Bio. Med. 84, 103–115.

    CAS  Article  Google Scholar 

  27. Xiong, M.Y.Y., Chen, G.Q., Zhou, W.H., 2009. Post-ischemic hypothermia for 24 h in P7 rats rescues hippocampal neuron, association with decreased astrocyte activation and inflammatory cytokine expression. Brain Res. Bull. 79, 351–357.

    CAS  Article  PubMed  Google Scholar 

  28. Yang, Y., Liu, P., Chen, L., Liu, Z., Zhang, H., Wang, J., 2013. Therapeutic effect of Ginkgo biloba polysaccharide in rats with focal cerebral ischemia/reperfusion (I/R) injury. Carbohyd. Polym. 98, 1383–1388.

    CAS  Article  Google Scholar 

  29. Yang, Z., Weian, C., Susu, H., Hanmin, W., 2016. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms. Eur. J. Pharmacol. 771, 145–151.

    CAS  Article  PubMed  Google Scholar 

  30. Yao, J., Xu, Y., Ji, F., Wang, C., Zhang, Y., Ni, J., Wang, R., 2011. Protective effects of MLIF analogs on cerebral ischemia-reperfusion injury in rats. Peptides 32, 1047–1054.

    CAS  Article  PubMed  Google Scholar 

  31. Ye, Y., Li, J., Cao, X., Chen, Y., Ye, C., Chen, It, 2016. Protective effect of n-butyl alcohol extracts from Rhizoma Pinelliae Pedatisectae against cerebral ischemia-reperfusion injury in rats. J. Ethnopharmacol. 188, 259–265.

    Article  PubMed  Google Scholar 

  32. Zhang, L., Zhang, X., Zhang, C., Bai, X., Zhang, J., Zhao, X., Chen, L., Wang, L., Zhu, C., Cui, L., Chen, R., Zhao, T., Zhao, Y., 2016. Nobiletin promotes antioxidant and anti-inflammatory responses and elicits protection against ischemic stroke in vivo. Brain Res. 1636, 130–141.

    CAS  Article  PubMed  Google Scholar 

  33. Zhang, S., Qi, Y., Xu, Y., Han, X., Peng, J., Liu, It, Sun, C.It, 2013. Protective effect of flavonoid-rich extract from Rosa laevigata Michx on cerebral ischemia-reperfusion injury through suppression of apoptosis and inflammation. Neurochem. Int. 63, 522–532.

    CAS  Article  PubMed  Google Scholar 

  34. Zhang, Y.B., Wang, X.F., Ma, L., Dong, L., Zhang, X.H., Chen, J., Fu, X.Y., 2014. Antiinflammatory, antinociceptive activity of an essential oil recipe consisting of the supercritical fluid CO2 extract of white pepper, long pepper, cinnamon, saffron and myrrh in vivo. J. Oleo Sci. 63, 1251–1260.

    CAS  Article  PubMed  Google Scholar 

  35. Zhao, Q., Cheng, X., Wang, X., Wang, J., Zhu, Y., Ma, X., 2016. Neuroprotective effect and mechanism of Mu-Xiang-You-Fang on cerebral ischemia-reperfusion injury in rats. J. Ethnopharmacol. 192, 140–147.

    Article  PubMed  Google Scholar 

  36. Zou, H., Long, J., Zhang, Q., Zhao, H., Bian, B., Wang, Y., 2016. Induced cortical neurogenesis after focal cerebral ischemia - three active components from Huang-Lian-Jie-Du decoction. J. Ethnopharmacol. 178, 115–124.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Xueyan Fu.

Additional information

Authors#x2019; contributions

BW and YZ contributed in collecting plant samples and conducting the laboratory work. JH contributed to the analysis of the data. LD and TL contributed to the critical reading of the manuscript. XF designed the study, supervised the laboratory work and contributed to the critical reading of the manuscript. All of the authors have read the final manuscript and approved its submission.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, B., Zhang, Y., Huang, J. et al. Anti-inflammatory activity and chemical composition of dichloromethane extract from Piper nigrum and P. longum on permanent focal cerebral ischemia injury in rats. Rev. Bras. Farmacogn. 27, 369–374 (2017). https://doi.org/10.1016/j.bjp.2017.02.003

Download citation

Keywords

  • Anti-inflammatory
  • HPLC
  • Permanent middle cerebral artery occlusion
  • Piperine