Bioaktivní látky šalvěje červenokořenné (Salvia miltiorrhiza Bunge) a jejich využití v medicíně

Bioactive substances of red sage (Salvia miltiorrhiza Bunge) and their use in medicine

Zdeňka Navrátilová1, Jiří Patočka2,, 3
1Univerzita Karlova v Praze, Přírodovědecká fakulta, katedra botaniky 2Jihočeská univerzita v Českých Budějovicích, Zdravotně sociální fakulta, katedra radiologie, toxikologie a ochrany obyvatelstva 3Fakultní nemocnice, Centrum biomedicínského výzkumu, Hradec Králové

Korespondenční autor: Zdeňka Navrátilová (navratil@natur.cuni.cz)

ISSN 1804-7858 (On-line)

Full verze:
Full version

Submitted:1. 8. 2013
Accepted: 14. 11. 2013
Published online: 20. 12. 2013

Summary

Red sage (Salvia miltiorrhiza Bunge) is a perennial herb of the family Lamiaceae (mint family) native to China, Japan, Mongolia and Korea. In traditional Eastern medicine, especially in Chinese, it has a variety of uses. For medicinal purposes it is grown commercially also in other countries. The root of the red sage is officially part of the Chinese Pharmacopoeia and is used both to prepare a beverage used internally, thus to prepare an ointment for external use. From the roots were isolated more than 90 various compounds subjected to biological testing. The lipophilic substances contained in the red sage mainly include diterpenic quinone compounds of the abietan type; the hydrophilic ones include polyphenols and phenolic acids. Their pharmacological effects are very varied: cardioprotective, antioxidant and anti-inflammatory, lipid-lowering, neuroprotective and hepatoprotective. In many cases, the pharmacological activity of the sage was associated with specific chemical substances that are responsible for biological activity. Modern plant research confirms that the effects attributed to the red sage in traditional medicine are based on pharmacologically active substances. Many of them are unique, they have not been found in other plants and they might be a model for the synthesis of similar substances with the expected pharmacological effect and promising application in biomedicine. This concerns especially the tanshinones, quinoid diterpenes that are recently intensively studied in particular as substances that effectively protect cells from apoptosis caused by hypoxia.

Keywords: red sage – Salvia miltiorrhiza – pharmacology – toxicology – biomedicine

Souhrn

Šalvěj červenokořenná (Salvia miltiorrhiza Bunge) je vytrvalá bylina z čeledi Lamiaceae (hluchavkovité) původem z Číny, Japonska, Mongolska a Koreje. V tradiční východní medicíně, zejména čínské, má mnohostranné využití. Pro medicinální účely se pěstuje komerčně i v jiných zemích. Kořen šalvěje červenokořenné je oficiální součástí čínského lékopisu a používá se jak k přípravě nápoje používaného vnitřně, tak k přípravě masti pro zevní použití. Z kořenů bylo izolováno již více než 90 různých sloučenin, které byly podrobeny biologickému testování. K lipofilním obsahovým látkám šalvěje červenokořenné patří především diterpenické chinonové sloučeniny abietanového typu, k těm hydrofilním polyfenoly a fenolické kyseliny. Jejich farmakologické účinky jsou velmi rozmanité: kardioprotektivní, antioxidační a protizánětlivé, protinádorové, hypolipidemické, neuroprotektivní a hepatoprotektivní. V mnoha případech byla farmakologická aktivita šalvěje spojena s konkrétními chemickými substancemi, které jsou za biologickou aktivitu zodpovědné.

Klíčová slova: šalvěj červenokořenná – Salvia miltiorrhiza – farmakologie – toxikologie – biomedicína

Literatura

  1. Abd-Elazem IS, Chen HS, Bates RB, Huang RC (2002). Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase from Salvia miltiorrhiza. Antiviral Res. 55/1: 91–106.
  2. Adams JD, Wang R, Yang J, Lien EJ (2006). Preclinical and clinical examinations of Salvia miltiorrhiza and its tanshinones in ischemic conditions. Chin Med. 23/1: 3.
  3. Alleva LM, Cai C, Clark IA (2010). Using complementary and alternative medicines to target the host response during severe influenza. Evid Based Complement Alternat Med. 7/4: 501–510.
  4. Bensky D, Clavey D, Stoger E (eds.) (2004). Chinese Herbal Medicine: Materia Medica 3rd ed. Eastland Press. 1311 p.
  5. Cao W, Guo XW, Zheng HZ, Li DP, Jia GB, Wang J (2012). Current progress of research on pharmacologic actions of salvianolic acid B. Chin J Integr Med. 18/4: 316–320.
  6. Ciccocioppo R, Economidou D, Cippitelli A, Cucculelli M, Ubaldi M, Soverchia L, Lourdusamy A, Massi M (2006). Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats: an animal model to study the neurobiology of alcoholism. Addict Biol. 11/3–4: 339–355.
  7. Colombo G, Serra S, Vacca G, Orrù A, Maccioni P, Morazzoni P, Bombardelli E, Riva A, Gessa GL, Carai MA (2006). Identification of miltirone as active ingredient of Salvia miltiorrhiza responsible for the reducing effect of root extracts on alcohol intake in rats. Alcohol Clin Exp Res. 30/5: 754–762.
  8. Hempen C-H (2009). A Materia Medica for Chinese Medicine: Plants, Minerals and Animal Products. Churchill Livingstone. 1016 p.
  9. Chang JY, Chang CY, Kuo CC, Chen LT, Wein YS, Kuo YH (2004). Salvinal, a novel microtubule inhibitor isolated from Salvia miltiorrhiza Bunge (Danshen), with antimitotic activity in multidrug-sensitive and -resistant human tumor cells. Mol Pharmacol. 65/1: 77–84.
  10. Imanshahidi M, Hosseinzadeh H (2006). The pharmacological effects of Salvia species on the central nervous system. Phytother Res. 20/6: 427–437.
  11. Ji XY, Tan BK, Zhu YZ (2000). Salvia miltiorrhiza and ischemic diseases. Acta Pharmacol Sin. 21/12: 1089–1094.
  12. Jiang RW, Lau KM, Hon PM, Mak TC, Woo KS, Fung KP (2005). Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza. Curr Med Chem. 12/2: 237–246.
  13. Jiang WY, Jeon BH, Kim YC, Lee SH, Sohn DH, Seo GS (2013). PF2401-SF, standardized fraction of Salvia miltiorrhiza shows anti-inflammatory activity in macrophages and acute arthritis in vivo. Int Immunopharmacol. 16/2: 160–164.
  14. Kamata K, Noguchi M, Nagai M (1994). Hypotensive effects of lithospermic acid B isolated from the extract of Salviae miltiorrhizae radix in the rat. Gen Pharmacol. 25/1: 69–73.
  15. Kang DG, Yun YG, Ryoo JH, Lee HS (2002). Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system. Am J Chin Med. 30/1: 87–93.
  16. Kang DG, Oh H, Chung HT, Lee HS (2003). Inhibition of angiotensin converting enzyme by lithospermic acid B isolated from Radix Salviae miltiorrhizae Bunge. Phytother Res. 17/8: 917–920.
  17. Koo BS, Kwon TS, Kim CH (2004). Salviae miltiorrhizae radix inhibits superoxide generation by activated rat microglias and mimics the action of amphetamine on in vitro rat striatal dopamine release. Neurochem Res. 29/10: 1837–1845.
  18. L ee CM, Wong HN, Chui KY, Choang TF, Hon PM, Chang HM (1991). Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza. Neurosci Lett. 127/2: 237–241.
  19. L ee JW, Ji YJ, Lee SO, Lee IS (2007). Effect of Salvia miltiorrhiza Bunge on antimicrobial activity and resistant

gene regulation against methicillin-resistant Staphylococcus aureus (MRSA). J Microbiol. 45/4: 350–357.

20. L ee TY, Mai LM, Wang GJ, Chiu JH, Lin YL, Lin HC (2003). Protective mechanism of Salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats. J Pharmacol Sci. 91/3: 202–210.

21. L iu P, Hu YY, Liu C, Zhu DY, Xue HM, Xu ZQ, Xu LM, Liu CH, Gu HT, Zhang ZQ (2002). Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B. World J Gastroenterol. 8/4: 679–685.

22. L u L, Liu Y, Zhang Z, Zhang H (2012). Analysis of Danshen and twelve related Salvia species. Nat Prod Commun. 7/1: 59–60.

23. Park JY, Kim JH, Kim YM, Jeong HJ, Kim DW, Park KH, Kwon HJ, Park SJ, Lee WS, Ryu YB (2012). Tanshinones as selective and slow-binding inhibitors for SARS-CoV cysteine proteases. Bioorg Med Chem. 20/19: 5928–5935.

24. Ren Y, Houghton PJ, Hider RC, Howes MJ (2004). Novel diterpenoid acetylcholines­terase inhibitors from Salvia miltiorhiza. Planta Med. 70/3: 201–204.

25. Shang Q, Xu H, Huang L (2012). Tanshinone IIA: A Promising Natural Cardioprotective Agent. Evid Based Complement Alternat Med. 2012: 716459. doi: 10.1155/2012/7­16459.

26. Song YH, Liu Q, Lv ZP, Chen YY, Zhou YC, Sun XG (2008). Protection of a polysaccharide from Salvia miltiorrhiza, a Chinese medicinal herb, against immunological liver injury in mice. Int J Biol Macromol. 43/2: 170–175.

27. Stafford L (2010). Chinese Herbal Medicine Clears US FDA Phase II Trials. HerbalEGram. [online] [cit. 2013–10–07]. Dostupné z: http://cms.herbalgram.org/…Itrials.html?…

28. Tang Y, Wang M, Chen C, Le X, Sun S, Yin Y (2011). Cardiovascular protection with danshensu in spontaneously hypertensive rats. Biol Pharm Bull. 34/10: 1596–1601.

29. Tsai MK, Lin YL, Huang YT (2010). Effects of salvianolic acids on oxidative stress and hepatic fibrosis in rats. Toxicol Appl Pharmacol. 242/2: 155–164.

30. Tung YT, Chen HL, Lee CY, Chou YC, Lee PY, Tsai HC, Lin YL, Chen CM (2013). Active Component of Danshen (Salvia miltiorrhiza Bunge), Tanshinone I, Attenuates Lung Tumorigenesis via Inhibitions of VEGF, Cyclin A, and Cyclin B Expressions. Evid Based Complement Alternat Med. 2013: 319247. doi: 10.1155/2013/3­19247.

31. Vacca G, Colombo G, Brunetti G, Melis S, Molinari D, Serra S, Seghizzi R, Morazzoni P, Bombardelli E, Gessa GL, Carai MA (2003). Reducing effect of Salvia miltiorrhiza extracts on alcohol intake: influence of vehicle. Phytother Res. 17/5: 537–541.

32. Valíček P, Ando V, Čížek H, Potužák M (1994). Léčivé rostliny tradiční čínské medicíny. Svítání, Hradec Králové. 321 s.

33. Wang X, Yeung JH (2012). Investigation of cytochrome P450 1A2 and 3A inhibitory properties of Danshen tincture. Phytomedicine. 19/3–4: 348–354.

34. Wang X, Morris-Natschke SL, Lee KH (2007). New developments in the chemistry and biology of the bioactive constituents of Tanshen. Med Res Rev. 27/1: 133–148.

35. Wang X, Cheung CM, Lee WY, Or PM, Yeung JH (2010). Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine. 17/11: 868–875.

36. Williamson EM (2005). Interactions between herbal and conventional medicines. Expert Opin Drug Saf. 4/2: 355–378.

37. Wong KK, Ho MT, Lin HQ, Lau KF, Rudd JA, Chung RC, Fung KP, Shaw PC, Wan DC (2010). Cryptotanshinone, an acetylcholines­terase inhibitor from Salvia miltiorrhiza, ameliorates scopolamine-induced amnesia in Morris water maze task. Planta Med. 76/3: 228–234.

38. Woo Lee Y, Hyun Kim D, Jin Jeon S, Jin Park S, Min Kim J, Man Jung J, Eun Lee H, Gil Bae S, Kyong Oh H, Ho Son K, Hoon Ryu J (2013). Neuroprotective effects of salvianolic acid B on an Aβ25–35 peptide-induced mouse model of Alzheimer’s di­sease. Eur J Pharmacol. 704/1–3: 70–77.

39. Wu BW, Pan TL, Leu YL, Chang YK, Tai PJ, Lin KH, Horng JT (2007a). Antiviral effects of Salvia miltiorrhiza (Danshen) against enterovirus 71. Am J Chin Med. 35/1: 153–168.

40. Wu B, Liu M, Zhang S (2007b). Dan Shen agents for acute ischaemic stroke. Cochrane Database Syst Rev. 2: CD004295.

41. Wu J-N (2005). An Illustrated Chinese Materia Medica. Oxford University Press. 706 p.

42. Wu ZM, Wen T, Tan YF, Liu Y, Ren F, Wu H (2007c). Effects of salvianolic acid a on oxidative stress and liver injury induced by carbon tetrachloride in rats. Basic Clin Pharmacol Toxicol. 100/2: 115–120.

43. Yan FF, Liu YF, Liu Y, Zhao YX (2009). Sulfotanshinone sodium injection could decrease fibrinogen level and improve clinical outcomes in patients with unstable angina pectoris. Int J Cardiol. 135/2: 254–255.

44. Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Duan W, Yu XQ, Wen JY, Chowbay B, Li CG, Sheu FS, Chan E, Zhou SF (2007). Tanshinone IIB, a primary active constituent from Salvia miltiorrhiza, exhibits neuro-protective activity in experimentally stroked rats. Neurosci Lett. 417/3: 261–265.

45. Yun SM, Jung JH, Jeong SJ, Sohn EJ, Kim B, Kim SH (2013). Tanshinone IIA Induces Autophagic Cell Death via Activation of AMPK and ERK and Inhibition of mTOR and p70 S6K in KBM-5 Leukemia Cells. Phytother Res. 2013. doi: 10.1002/ptr.5015.

46. Zhang W, Lu Y (2010). Advances in studies on antitumor activities of compounds in Salvia miltiorrhiza. Zhongguo Zhong Yao Za Zhi. 35/3: 389–392. [article in Chinese]

47. Zhang Y, Jiang P, Ye M, Kim SH, Jiang C, Lü J (2012). Tanshinones: sources, pharmacokinetics and anti-cancer activities. Int J Mol Sci. 13/10: 13621–13666. 48. Zhao J, Lou J, Mou Y, Li P, Wu J, Zhou L (2011). Diterpenoid tanshinones and phenolic acids from cultured hairy roots of Salvia miltiorrhiza Bunge and their antimicrobial activities. Molecules. 16/3: 2259–2267.

49. Zhengyi W, Raven PH (eds.) (1994). Flora of China Vol. 17. Verbenaceae through Solanaceae. Missouri Botanical Press. 378 p.

50. Zhou L, Zuo Z, Chow MS (2005). Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol. 45/12: 1345–1359.

51. Zhou Z, Zhang Y, Ding XR, Chen SH, Yang J, Wang XJ, Jia GL, Chen HS, Bo XC, Wang SQ (2007). Protocatechuic aldehyde inhibits hepatitis B virus replication both in vitro and in vivo. Antiviral Res. 74/1: 59–64.