Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma lucidum (Curtis) P. Karst

BMC Complementary and Alternative Medicine

Norhaniza Aminudin³  Noorlidah Abdullah¹  Nurhuda Mohamad Ansor² 

[1] Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia;Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bandar Putra Bertam, Kepala Batas 13200, Penang, Malaysia;University of Malaya Centre for Proteomics Research, University of Malaya, Kuala Lumpur 50603, Malaysia

关键词: MALDI-TOF/TOF MS;    Hypertension;    Lingzhi;    Bioactive peptides/proteins;    ACE inhibitory proteins;   

Others  :  1220904
DOI  :  10.1186/1472-6882-13-256

 received in 2013-05-21, accepted in 2013-09-17,  发布年份 2013

【 摘 要 】

Background

Ganoderma lucidum has been purported as a potent remedy in the treatment and prevention of several ailments, including hypertension. This study aimed to explore the anti-ACE potential of protein fractions from the mycelia of G. lucidum.

Methods

Ganoderma lucidum mycelia were cultivated by submerged fermentation in a liquid medium containing brown sugar and spent brewer’s yeast. Intracellular proteins were fractionated from mycelia crude water extract by ammonium sulphate precipitation, and their angiotensin converting enzyme inhibitory activity was evaluated. The potential anti-ACE protein fractions were further separated by RP-HPLC and characterised using proteomics platforms.

Results

Preliminary result demonstrated that the mycelia crude water extract inhibited ACE at IC₅₀ value of 1.134 ± 0.036 mg/mL. Following protein fractionation and HPLC purification, the presence of highly potential anti-ACE proteins with the IC₅₀ values less than 200 μg/mL was detected. Characterisation of these proteins demonstrated the presence of four different antihypertensive-related proteins involved in the regulation of blood pressure through different mechanisms.

Conclusions

This study suggests that the mycelia of G. lucidum has high potential in lowering blood pressure level due to the presence of several antihypertensive-related proteins such as cystathionine beta synthase-like protein, DEAD/DEAH box helicase-like protein, paxillin-like protein, and alpha/beta hydrolase-like protein.

【 授权许可】

   
2013 Mohamad Ansor et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]World Health Organization: Global status report on noncommunicable diseases 2010. Geneva: WHO Press; 2011.
• [2]Erdös EG: Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture. Hypertension 1990, 16:363-370.
• [3]Cushman DW, Ondetti MA: Design of angiotensin converting enzyme inhibitors. Nat Med 1999, 5:1110-1112.
• [4]Hernandez AF, Harrington RA: Comparative effectiveness of angiotensin converting enzyme inhibitors: is an ACE always an ace? Can Med Assoc J 2008, 178:1316-1319.
• [5]Reid JL: From kinetics to dynamics: are there differences between ACE inhibitors? Eur Heart J 1997, 18(Suppl E):E14-E18.
• [6]Mukae S, Aoki S, Itoh S, Iwata T, Ueda H, Katagiri T: Bradykinin B2 receptor gene polymorphism is associated with angiotensin-converting enzyme inhibitor–related cough. Hypertension 2000, 36:127-131.
• [7]Hong F, Ming L, Yi S, Zhanxia L, Yongquan W, Chi L: The antihypertensive effect of peptides: a novel alternative to drugs? Peptides 2008, 29:1062-1071.
• [8]Elliott P, Stamler J, Dyer AR, Appel L, Dennis B, Kesteloot H, Ueshima H, Okayama A, Chan Q, Garside DB, Zhou B: Association between protein intake and blood pressure: the INTERMAP study. AMA Arch Intern Med 2006, 166:79-87.
• [9]Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, Bisen PS: Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol 2009, 10:717-742.
• [10]Aminudin N, Abdullah NAH, Misbah H, Karsani SA, Husain R, Hoe SZ, Hashim OH: Treatment with captopril abrogates the altered expression of alpha1 macroglobulin and alpha1 antiproteinase in sera of spontaneously hypertensive rats. Proc Natl Acad Sci U S A 2012, 10:17.
• [11]Gao XJ, Yan PS, Wang JB, Yu JJ: ACE inhibitory, antitumor and antioxidant activities of submerged culture materials of three medicinal mushrooms. Appl Mech Mater 2012, 145:179-183.
• [12]Wu J, Aluko RE, Nakai S: Structural requirements of angiotensin I-converting enzyme inhibitory peptides: quantitative structure-activity relationship study of di- and tripeptides. J Agric Food Chem 2006, 54:732-738.
• [13]Choi HS, Cho HY, Yang HC, Ra KS, Suh HJ: Angiotensin I-converting enzyme inhibitor from Grifola frondosa. Food Res Int 2001, 34:177-182.
• [14]Lee DH, Kim JH, Park JS, Choi YJ, Lee JS: Isolation and characterization of a novel angiotensin I-converting enzyme inhibitory peptide derived from the edible mushroom Tricholoma giganteum. Peptides 2004, 25:621-627.
• [15]Koo KC, Lee DH, Kim JH, Yu HE, Park JS, Lee JS: Production and characterization of antihypertensive angiotensin I-converting enzyme inhibitor from Pholiota adiposa. J Microbiol Biotechnol 2006, 16:757-763.
• [16]Raghavan S, Kristinsson HG: ACE-inhibitory activity of tilapia protein hydrolysates. Food Chem 2009, 117:582-588.
• [17]McHugh L, Arthur JW: Computational methods for protein identification from mass spectrometry data. PLoS Comput Biol 2008, 4(2):e12.
• [18]Zhang W, Chait BT: ProFound: an expert system for protein identification using mass spectrometric peptide mapping information. Anal Chem 2000, 72:2482-2489.
• [19]Proudfoot M, Sanders SA, Singer A, Zhang R, Brown G, Binkowski A, Xu L, Lukin JA, Murzin AG, Joachimiak A, Arrowsmith CH, Edwards AM, Savchencko AV, Yakunin AF: Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain. J Mol Biol 2008, 375:301-315.
• [20]Treich I, Riva M, Sentenac A: Zinc-binding subunits of yeast RNA polymerases. J Biol Chem 1991, 266:21971-21976.
• [21]Natesh R, Schwager SL, Sturrock ED, Acharya KR: Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature 2003, 421:551-554.
• [22]Sahni A, Wang N, Alexis JD: UAP56 is an important regulator of protein synthesis and growth in cardiomyocytes. Biochem Biophys Res Commun 2010, 393:106-110.
• [23]Liu ZP, Olson EN: Suppression of proliferation and cardiomyocyte hypertrophy by CHAMP, a cardiac-specific RNA helicase. Proc Natl Acad Sci 2002, 99:2043-2048.
• [24]Xiaozhen H, Yun Z, Mei Z, Yu S: Effect of carvedilol on coronary flow reserve in patients with hypertensive leftventricular hypertrophy. Blood Press 2010, 19:40-47.
• [25]Bukharova T, Weijer G, Bosgraaf L, Dormann D, Van-Haastert PJ, Weijer CJ: Paxillin is required for cell-substrate adhesion, cell sorting and slug migration during Dictyostelium development. J Cell Sci 2005, 118:4295-4310.
• [26]Tang DD, Anfinogenova Y: Physiologic properties and regulation of the actin cytoskeleton in vascular smooth muscle. J Cardiovasc Pharmacol Ther 2008, 13:130-140.
• [27]Lee DL, Webb RC, Jin L: Hypertension and RhoA/Rho-kinase signaling in the vasculature: highlights from the recent literature. Hypertension 2004, 44:796-799.
• [28]Sinal CJ, Miyata M, Tohkin M, Nagata K, Bend JR, Gonzalez FJ: Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation. J Biol Chem 2000, 275:40504-40510.
• [29]Yu Z, Xu F, Huse LM, Morisseau C, Draper AJ, Newman JW, Parker C, Graham L, Engler MM, Hammock BD, Zeldin DC, Kroetz DL: Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids. Circ Res 2000, 87:992-998.
• [30]Fang X, Kaduce TL, Weintraub NL, Harmon S, Teesch LM, Morisseau C, Thompson DA, Hammock BD, Spector AA: Pathways of epoxyeicosatrienoic acid metabolism in endothelial cells: implications for the vascular effects of soluble epoxide hydrolase inhibition. J Biol Chem 2001, 276:14867-14874.