Herbal Medicine for Slowing Aging and Aging-associated Conditions: Efficacy, Mechanisms and Safety

Author(s): Hoa T. Phu, Duong T.B. Thuan, Thi H.D. Nguyen, Anna M. Posadino, Ali H. Eid*, Gianfranco Pintus*

Journal Name: Current Vascular Pharmacology

Volume 18 , Issue 4 , 2020

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Graphical Abstract:


Abstract:

Aging and aging-associated diseases are issues with unsatisfactory answers in the medical field. Aging causes important physical changes which, even in the absence of the usual risk factors, render the cardiovascular system prone to some diseases. Although aging cannot be prevented, slowing down the rate of aging is entirely possible to achieve. In some traditional medicine, medicinal herbs such as Ginseng, Radix Astragali, Ganoderma lucidum, Ginkgo biloba, and Gynostemma pentaphyllum are recognized by the “nourishing of life” and their role as anti-aging phytotherapeutics is increasingly gaining attention. By mainly employing PubMed here we identify and critically analysed 30 years of published studies focusing on the above herbs' active components against aging and aging-associated conditions. Although many plant-based compounds appear to exert an anti-aging effect, the most effective resulted in being flavonoids, terpenoids, saponins, and polysaccharides, which include astragaloside, ginkgolide, ginsenoside, and gypenoside specifically covered in this review. Their effects as antiaging factors, improvers of cognitive impairments, and reducers of cardiovascular risks are described, as well as the molecular mechanisms underlying the above-mentioned effects along with their potential safety. Telomere and telomerase, PPAR-α, GLUTs, FOXO1, caspase-3, bcl-2, along with SIRT1/AMPK, PI3K/Akt, NF-κB, and insulin/insulin-like growth factor-1 pathways appear to be their preferential targets. Moreover, their ability to work as antioxidants and to improve the resistance to DNA damage is also discussed. Although our literature review indicates that these traditional herbal medicines are safe, tolerable, and free of toxic effects, additional well-designed, large-scale randomized control trials need to be performed to evaluate short- and long-term effects and efficacy of these medicinal herbs.

Keywords: Herbal medicine, aging, cardiovascular diseases, cognitive impairment, metabolic disorders, elderly, traditional medicine, signaling, signal transduction, antioxidants, oxidative stress, inflammation.

[1]
Frasca D, Blomberg BB, Paganelli R. Aging, obesity, and inflammatory age-related diseases. Front Immunol 2017; 8: 1745.
[http://dx.doi.org/10.3389/fimmu.2017.01745] [PMID: 29270179]
[2]
Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 2018; 13: 757-72.
[http://dx.doi.org/10.2147/CIA.S158513] [PMID: 29731617]
[3]
Rattan SI. Aging is not a disease: implications for intervention. Aging Dis 2014; 5(3): 196-202.
[http://dx.doi.org/10.14336/AD.2014.0500196] [PMID: 24900942]
[4]
Costantino S, Paneni F, Cosentino F. Ageing, metabolism and cardiovascular disease. J Physiol 2016; 594(8): 2061-73.
[http://dx.doi.org/10.1113/JP270538] [PMID: 26391109]
[5]
North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res 2012; 110(8): 1097-108.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.246876] [PMID: 22499900]
[6]
Leritz EC, McGlinchey RE, Kellison I, Rudolph JL, Milberg WP. Cardiovascular disease risk factors and cognition in the elderly. Curr Cardiovasc Risk Rep 2011; 5(5): 407-12.
[http://dx.doi.org/10.1007/s12170-011-0189-x] [PMID: 22199992]
[7]
Knopman D, Boland LL, Mosley T, et al. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001; 56(1): 42-8.
[http://dx.doi.org/10.1212/WNL.56.1.42] [PMID: 11148234]
[8]
Grodstein F. Cardiovascular risk factors and cognitive function. Alzheimers Dement 2007; 3(2): 16-22.
[http://dx.doi.org/10.1016/j.jalz.2007.01.001] [PMID: 19595969]
[9]
Anderson AL, Harris TB, Tylavsky FA, et al. Dietary patterns and survival of older adults. J Am Diet Assoc 2011; 111(1): 84-91.
[http://dx.doi.org/10.1016/j.jada.2010.10.012] [PMID: 21185969]
[10]
Saleh Al-Shehabi T, Iratni R, Eid AH. Anti-atherosclerotic plants which modulate the phenotype of vascular smooth muscle cells. Phytomedicine 2016; 23(11): 1068-81.
[http://dx.doi.org/10.1016/j.phymed.2015.10.016] [PMID: 26776961]
[11]
Anwar MA, Al Disi SS, Eid AH. Anti-hypertensive herbs and their mechanisms of action: part II. Front Pharmacol 2016; 7: 50.
[http://dx.doi.org/10.3389/fphar.2016.00050] [PMID: 27014064]
[12]
Liu C, Huang Y. Chinese herbal hedicine on cardiovascular diseases and the mechanisms of action. Front Pharmacol 2016; 7: 469.
[http://dx.doi.org/10.3389/fphar.2016.00469] [PMID: 27990122]
[13]
Cheung B, Kwan M, Chan R, Sea M, Woo J. Potential of Asian natural products for health in aging: Molecular Nutrition Series. Elsevier Inc. 2016.
[http://dx.doi.org/10.1016/B978-0-12-801816-3.00047-9]
[14]
Bent S. Herbal medicine in the United States: review of efficacy, safety, and regulation: grand rounds at University of California, San Francisco Medical Center. J Gen Intern Med 2008; 23(6): 854-9.
[http://dx.doi.org/10.1007/s11606-008-0632-y] [PMID: 18415652]
[15]
Shih-Chen L, Smith F, Stuart G. Chinese medicinal herbs. Georgetown Press, San Fransico 1973.
[16]
Kim WY, Kim JM, Han SB, et al. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod 2000; 63(12): 1702-4.
[http://dx.doi.org/10.1021/np990152b] [PMID: 11141123]
[17]
Mahady GB, Gyllenhaal C, Fong HH, Farnsworth NR. Ginsengs: a review of safety and efficacy. Nutr Clin Care 2000; 3: 90-101.
[http://dx.doi.org/10.1046/j.1523-5408.2000.00020.x]
[18]
Lee CH, Kim JH. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 2014; 38(3): 161-6.
[http://dx.doi.org/10.1016/j.jgr.2014.03.001] [PMID: 25378989]
[19]
Kim JH. Cardiovascular diseases and panax ginseng: A review on molecular mechanisms and medical applications. J Ginseng Res 2012; 36(1): 16-26.
[http://dx.doi.org/10.5142/jgr.2012.36.1.16] [PMID: 23717100]
[20]
Ho YS, So KF, Chang RC. Anti-aging herbal medicine--how and why can they be used in aging-associated neurodegenerative diseases? Ageing Res Rev 2010; 9(3): 354-62.
[http://dx.doi.org/10.1016/j.arr.2009.10.001] [PMID: 19833234]
[21]
Lü JM, Weakley SM, Yang Z, Hu M, Yao Q, Chen C. Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid. Curr Pharm Des 2012; 18(38): 6339-47.
[http://dx.doi.org/10.2174/138161212803832254] [PMID: 22974003]
[22]
Kitts DD, Wijewickreme AN, Hu C. Antioxidant properties of a North American ginseng extract. Mol Cell Biochem 2000; 203(1-2): 1-10.
[http://dx.doi.org/10.1023/A:1007078414639] [PMID: 10724326]
[23]
Fu Y, Ji LL. Chronic ginseng consumption attenuates age-associated oxidative stress in rats. J Nutr 2003; 133(11): 3603-9.
[http://dx.doi.org/10.1093/jn/133.11.3603] [PMID: 14608081]
[24]
Lee H, Hong Y, Tran Q, et al. A new role for the ginsenoside RG3 in antiaging via mitochondria function in ultraviolet-irradiated human dermal fibroblasts. J Ginseng Res 2019; 43(3): 431-41.
[http://dx.doi.org/10.1016/j.jgr.2018.07.003] [PMID: 31308815]
[25]
Tsang KH, Cheung HY. Recent studies of anti-aging herbs: the biomedical functions of gingko, lycium barbarum fruitus and ginseng. Hong Kong Pharml J 2014; 21: 65-71.
[26]
Song X, Bao M, Li D, Li YM. Advanced glycation in D-galactose induced mouse aging model. Mech Ageing Dev 1999; 108(3): 239-51.
[http://dx.doi.org/10.1016/S0047-6374(99)00022-6] [PMID: 10405984]
[27]
Zhu JD, Wang JJ, Zhang XH, Yu Y, Kang ZS. Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion. Neural Regen Res 2018; 13(4): 664-72.
[http://dx.doi.org/10.4103/1673-5374.230292] [PMID: 29722318]
[28]
Zhu J, Mu X, Zeng J, et al. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of D-galactose-induced aging. PLoS One 2014; 9(6) e101291
[http://dx.doi.org/10.1371/journal.pone.0101291] [PMID: 24979747]
[29]
Wang T, Di G, Yang L, et al. Saponins from Panax japonicus attenuate D-galactose-induced cognitive impairment through its anti-oxidative and anti-apoptotic effects in rats. J Pharm Pharmacol 2015; 67(9): 1284-96.
[http://dx.doi.org/10.1111/jphp.12413] [PMID: 25892055]
[30]
Cervantes Gracia K, Llanas-Cornejo D, Husi H. CVD and Oxidative Stress. J Clin Med 2017; 6(2): 22.
[http://dx.doi.org/10.3390/jcm6020022] [PMID: 28230726]
[31]
Wang Z, Zhang H. Antidiabetic effects of ginseng in humans and rodents. J Metab Syndr 2012; 1: 106.
[http://dx.doi.org/10.4172/2167-0943.1000106]
[32]
Shishtar E, Sievenpiper JL, Djedovic V, et al. The effect of ginseng (the genus panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials. PLoS One 2014; 9(9) e107391
[http://dx.doi.org/10.1371/journal.pone.0107391] [PMID: 25265315]
[33]
Abdelazim A, Khater S, Ali H, et al. Panax ginseng improves glucose metabolism in streptozotocin-induced diabetic rats through 5′ adenosine monophosphate kinase up-regulation. Saudi J Biol Sci 2019; 26(7): 1436-41.
[PMID: 31762606]
[34]
Singh RK, Lui E, Wright D, Taylor A, Bakovic M. Alcohol extract of North American ginseng (Panax quinquefolius) reduces fatty liver, dyslipidemia, and other complications of metabolic syndrome in a mouse model. Can J Physiol Pharmacol 2017; 95(9): 1046-57.
[http://dx.doi.org/10.1139/cjpp-2016-0510] [PMID: 28666094]
[35]
Mollah ML, Kim GS, Moon HK, et al. Antiobesity effects of wild ginseng (Panax ginseng C.A. Meyer) mediated by PPAR-γ, GLUT4 and LPL in ob/ob mice. Phytother Res 2009; 23(2): 220-5.
[http://dx.doi.org/10.1002/ptr.2593] [PMID: 18830966]
[36]
Song B, Ding L, Zhang H, et al. Ginsenoside Rb1 increases insulin sensitivity through suppressing 11β-hydroxysteroid dehydrogenase type I. Am J Transl Res 2017; 9(3): 1049-57.
[PMID: 28386332]
[37]
Jiang S, Ren D, Li J, et al. Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus. Fitoterapia 2014; 95: 58-64.
[http://dx.doi.org/10.1016/j.fitote.2014.02.017] [PMID: 24613802]
[38]
Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 2009; 9(5): 407-16.
[http://dx.doi.org/10.1016/j.cmet.2009.03.012] [PMID: 19416711]
[39]
Qureshi AA, Abuirmeileh N, Din ZZ, Ahmad Y, Burger WC, Elson CE. Suppression of cholesterogenesis and reduction of LDL cholesterol by dietary ginseng and its fractions in chicken liver. Atherosclerosis 1983; 48(1): 81-94.
[http://dx.doi.org/10.1016/0021-9150(83)90019-9] [PMID: 6882511]
[40]
Yamamoto M, Uemura T, Nakama S, Uemiya M, Kumagai A. Serum HDL-cholesterol-increasing and fatty liver-improving actions of Panax ginseng in high cholesterol diet-fed rats with clinical effect on hyperlipidemia in man. Am J Chin Med 1983; 11(1-4): 96-101.
[http://dx.doi.org/10.1142/S0192415X83000161] [PMID: 6660221]
[41]
Deng J, Liu Y, Duan Z, et al. Protopanaxadiol and protopanaxatriol-type saponins ameliorate glucose and lipid metabolism in type 2 diabetes mellitus in high-fat diet/streptozocin-induced mice. Front Pharmacol 2017; 8: 506.
[http://dx.doi.org/10.3389/fphar.2017.00506] [PMID: 28824430]
[42]
Shin SS, Yoon M. Korean red ginseng (Panax ginseng) inhibits obesity and improves lipid metabolism in high fat diet-fed castrated mice. J Ethnopharmacol 2018; 210: 80-7.
[http://dx.doi.org/10.1016/j.jep.2017.08.032] [PMID: 28844680]
[43]
Kim SH, Park KS. Effects of Panax ginseng extract on lipid metabolism in humans. Pharmacol Res 2003; 48(5): 511-3.
[http://dx.doi.org/10.1016/S1043-6618(03)00189-0] [PMID: 12967598]
[44]
Park MY, Lee KS, Sung MK. Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions. Life Sci 2005; 77(26): 3344-54.
[http://dx.doi.org/10.1016/j.lfs.2005.05.043] [PMID: 15979095]
[45]
Yang J-W, Kim SS. Ginsenoside Rc promotes anti-adipogenic activity on 3T3-L1 adipocytes by down-regulating C/EBPα and PPARγ. Molecules 2015; 20(1): 1293-303.
[http://dx.doi.org/10.3390/molecules20011293] [PMID: 25594343]
[46]
Oh J, Lee H, Park D, Ahn J, Shin SS, Yoon M. Ginseng and its active components ginsenosides inhibit adipogenesis in 3T3-L1 cells by regulating MMP-2 and MMP-9. Evid Based Complement Alternat Med 2012; 2012 265023
[http://dx.doi.org/10.1155/2012/265023] [PMID: 23258984]
[47]
Park J-H, Lee J-Y, Yeo J-Y, Nam J-S, Jung M-H. Antihyperlipidemic effect of ginsenoside Rg1 in type 2 diabetic mice. J Life Sci (Calicut) 2011; 21: 932-8.
[http://dx.doi.org/10.5352/JLS.2011.21.7.932]
[48]
Park JB, Kwon SK, Nagar H, et al. Rg3-enriched Korean Red Ginseng improves vascular function in spontaneously hypertensive rats. J Ginseng Res 2014; 38(4): 244-50.
[http://dx.doi.org/10.1016/j.jgr.2014.05.011] [PMID: 25379003]
[49]
Persson IA, Dong L, Persson K. Effect of Panax ginseng extract (G115) on angiotensin-converting enzyme (ACE) activity and nitric oxide (NO) production. J Ethnopharmacol 2006; 105(3): 321-5.
[http://dx.doi.org/10.1016/j.jep.2005.10.030] [PMID: 16387458]
[50]
Mucalo I, Jovanovski E, Rahelić D, Božikov V, Romić Z, Vuksan V. Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J Ethnopharmacol 2013; 150(1): 148-53.
[http://dx.doi.org/10.1016/j.jep.2013.08.015] [PMID: 23973636]
[51]
Jovanovski E, Bateman EA, Bhardwaj J, et al. Effect of Rg3-enriched Korean red ginseng (Panax ginseng) on arterial stiffness and blood pressure in healthy individuals: a randomized controlled trial. J Am Soc Hypertens 2014; 8(8): 537-41.
[http://dx.doi.org/10.1016/j.jash.2014.04.004] [PMID: 24997863]
[52]
Shin W, Yoon J, Oh GT, Ryoo S. Korean red ginseng inhibits arginase and contributes to endotheliumdependent vasorelaxation through endothelial nitric oxide synthase coupling. J Ginseng Res 2013; 37(1): 64-73.
[http://dx.doi.org/10.5142/jgr.2013.37.64] [PMID: 23717158]
[53]
Durgnat JM, Heuser J, Andrey D, Perrin C. Quality and safety assessment of ginseng extracts by determination of the contents of pesticides and metals. Food Addit Contam 2005; 22(12): 1224-30.
[http://dx.doi.org/10.1080/02652030500199439] [PMID: 16356886]
[54]
Park KS, Park KI, Kim JW, et al. Efficacy and safety of Korean red ginseng for cold hypersen-sitivity in the hands and feet: a randomized, double-blind, placebo-controlled trial. J Ethnopharmacol 2014; 158(Pt A): 25-32.
[55]
Shergis JL, Zhang AL, Zhou W, Xue CC. Panax ginseng in randomised controlled trials: a systematic review. Phytother Res 2013; 27(7): 949-65.
[http://dx.doi.org/10.1002/ptr.4832] [PMID: 22969004]
[56]
Murthy HN, Dandin VS, Park SY, Paek KY. Quality, safety and efficacy profiling of ginseng adventitious roots produced in vitro. Appl Microbiol Biotechnol 2018; 102(17): 7309-17.
[http://dx.doi.org/10.1007/s00253-018-9188-x] [PMID: 29971477]
[57]
Lee NH, Yoo SR, Kim HG, Cho JH, Son CG. Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers. J Altern Complement Med 2012; 18(11): 1061-9.
[http://dx.doi.org/10.1089/acm.2011.0591] [PMID: 22909282]
[58]
Shishtar E, Jovanovski E, Jenkins A, Vuksan V. Effects of Korean white ginseng (Panax Ginseng CA Meyer) on vascular and glycemic health in type 2 diabetes: results of a randomized, double blind, placebo-controlled, multiple-crossover, acute dose escalation trial. Clin Nutr Res 2014; 3(2): 89-97.
[http://dx.doi.org/10.7762/cnr.2014.3.2.89] [PMID: 25136536]
[59]
Song SW, Kim HN, Shim JY, et al. Safety and tolerability of Korean Red Ginseng in healthy adults: a multicenter, double-blind, randomized, placebo-controlled trial. J Ginseng Res 2018; 42(4): 571-6.
[http://dx.doi.org/10.1016/j.jgr.2018.07.002] [PMID: 30337818]
[60]
Liu Q, Zhang FG, Zhang WS, et al. Ginsenoside Rg1 Inhibits glucagon-induced hepatic gluconeogenesis through Akt-FoxO1 interaction. Theranostics 2017; 7(16): 4001-12.
[http://dx.doi.org/10.7150/thno.18788] [PMID: 29109794]
[61]
Meng F, Su X, Li W, Zheng Y. Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis. Exp Ther Med 2017; 13(5): 2551-7.
[http://dx.doi.org/10.3892/etm.2017.4280] [PMID: 28565878]
[62]
Wei S, Li W, Yu Y, et al. Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: A study in vitro and in vivo. Life Sci 2015; 139: 8-15.
[http://dx.doi.org/10.1016/j.lfs.2015.07.032] [PMID: 26285176]
[63]
Xiao N, Lou MD, Lu YT, et al. Ginsenoside Rg5 attenuates hepatic glucagon response via suppression of succinate-associated HIF-1α induction in HFD-fed mice. Diabetologia 2017; 60(6): 1084-93.
[http://dx.doi.org/10.1007/s00125-017-4238-y] [PMID: 28280902]
[64]
Belwal T, Giri L, Bahukhandi A, et al. Ginkgo biloba In: nonvitamin and nonmineral nutritional supplements. Publisher: Elsevier Inc. 1995.
[65]
Kleijnen J, Knipschild P. Ginkgo biloba. Lancet 1992; 340(8828): 1136-9.
[http://dx.doi.org/10.1016/0140-6736(92)93158-J] [PMID: 1359218]
[66]
Chan PC, Xia Q, Fu PP. Ginkgo biloba leave extract: biological, medicinal, and toxicological effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007; 25(3): 211-44.
[http://dx.doi.org/10.1080/10590500701569414] [PMID: 17763047]
[67]
Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 2007; 292(1): R18-36.
[http://dx.doi.org/10.1152/ajpregu.00327.2006] [PMID: 16917020]
[68]
Droy-Lefaix MT. Effect of the antioxidant action of Ginkgo biloba extract (EGb 761) on aging and oxidative stress. Age (Omaha) 1997; 20(3): 141-9.
[http://dx.doi.org/10.1007/s11357-997-0013-1] [PMID: 23604306]
[69]
Tiedtke J, Marks O. Multi-functional botanical active based on ginko for anti-aging. Cosmetic Sci Technol 2005; 2005: 18-25.
[70]
Wang TY, Li Q, Bi KS. Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian J Pharm Sci 2018; 13(1): 12-23.
[http://dx.doi.org/10.1016/j.ajps.2017.08.004] [PMID: 32104374]
[71]
Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res 2001; 15(5): 449-51.
[http://dx.doi.org/10.1002/ptr.814] [PMID: 11507743]
[72]
Diamond BJ, Shiflett SC, Feiwel N, et al. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000; 81(5): 668-78.
[http://dx.doi.org/10.1016/S0003-9993(00)90052-2] [PMID: 10807109]
[73]
Abdel-Kader R, Hauptmann S, Keil U, et al. Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761). Pharmacol Res 2007; 56(6): 493-502.
[http://dx.doi.org/10.1016/j.phrs.2007.09.011] [PMID: 17977008]
[74]
Shi C, Xiao S, Liu J, et al. Ginkgo biloba extract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice. Platelets 2010; 21(5): 373-9.
[http://dx.doi.org/10.3109/09537100903511448] [PMID: 20459350]
[75]
Aydin Y. Antiaging strategies based on telomerase activity. In: Molecular basis and emerging strategies for anti-aging interventions. Springer Singapore 1995; pp. 97-109.
[76]
Dong XX, Hui ZJ, Xiang WX, Rong ZF, Jian S, Zhu CJ. Ginkgo biloba extract reduces endothelial progenitor-cell senescence through augmentation of telomerase activity. J Cardiovasc Pharmacol 2007; 49(2): 111-5.
[http://dx.doi.org/10.1097/FJC.0b013e31802ef519] [PMID: 17312453]
[77]
Darlington CL, Smith PF, Maclennan K. The neuroprotective properties of ginkgo extracts: Ginkgo biloba. Amsterdam: Hardwood Academic 2000; pp. 331-44.
[78]
Schulz J, Halama P, Hoerr R. Ginkgo biloba extracts for the treatment of cerebral insufficiency and dementia Ginkgo biloba. Amsterdam: Harwood Academic 2000; pp. 345-70.
[79]
Ramassamy C, Longpré F, Christen Y. Ginkgo biloba extract (EGb 761) in Alzheimer’s disease: is there any evidence? Curr Alzheimer Res 2007; 4(3): 253-62.
[http://dx.doi.org/10.2174/156720507781077304] [PMID: 17627482]
[80]
Oyama Y, Chikahisa L, Ueha T, Kanemaru K, Noda K. Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Res 1996; 712(2): 349-52.
[http://dx.doi.org/10.1016/0006-8993(95)01440-3] [PMID: 8814913]
[81]
Koç RK, Akdemir H, Kurtsoy A, et al. Lipid peroxidation in experimental spinal cord injury. Comparison of treatment with Ginkgo biloba, TRH and methylprednisolone. Res Exp Med (Berl) 1995; 195(2): 117-23.
[http://dx.doi.org/10.1007/BF02576781] [PMID: 7659833]
[82]
Ni Y, Zhao B, Hou J, Xin W. Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals. Neurosci Lett 1996; 214(2-3): 115-8.
[http://dx.doi.org/10.1016/0304-3940(96)12897-4] [PMID: 8878097]
[83]
Bastianetto S, Ramassamy C, Doré S, Christen Y, Poirier J, Quirion R. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci 2000; 12(6): 1882-90.
[http://dx.doi.org/10.1046/j.1460-9568.2000.00069.x] [PMID: 10886329]
[84]
Yao ZX, Han Z, Drieu K, Papadopoulos V. Ginkgo biloba extract (Egb 761) inhibits beta-amyloid production by lowering free cholesterol levels. J Nutr Biochem 2004; 15(12): 749-56.
[http://dx.doi.org/10.1016/j.jnutbio.2004.06.008] [PMID: 15607648]
[85]
Luo Y, Smith JV, Paramasivam V, et al. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci USA 2002; 99(19): 12197-202.
[http://dx.doi.org/10.1073/pnas.182425199] [PMID: 12213959]
[86]
Zhang LD, Ma L, Zhang L, et al. Hyperbaric oxygen and Ginkgo biloba extract ameliorate cognitive and memory impairment via Nuclear Factor Kappa-B pathway in rat model of Alzheimer’s disease. Chin Med J (Engl) 2015; 128(22): 3088-93.
[http://dx.doi.org/10.4103/0366-6999.169105] [PMID: 26608991]
[87]
Robertson RP, Tanaka Y, Takahashi H, Tran PO, Harmon JS. Prevention of oxidative stress by adenoviral overexpression of glutathione-related enzymes in pancreatic islets. Ann N Y Acad Sci 2005; 1043: 513-20.
[http://dx.doi.org/10.1196/annals.1333.058] [PMID: 16037273]
[88]
Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010; 107(9): 1058-70.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]
[89]
Cheng D, Liang B, Li Y. Antihyperglycemic effect of Ginkgo biloba extract in streptozotocin-induced diabetes in rats. BioMed Res Int 2013; 2013 162724
[http://dx.doi.org/10.1155/2013/162724] [PMID: 23509685]
[90]
Li X, Hu Y, Fu Y, Ying Y, Chen G. [Effect of Ginkgo biloba extract on glucose uptake of diaphragm in diabetic rats]. Zhongguo Zhongyao Zazhi 2010; 35(3): 356-9.
[PMID: 20423005]
[91]
Löffler T, Lee SK, Nöldner M, Chatterjee SS, Hoyer S, Schliebs R. Effect of Ginkgo biloba extract (EGb761) on glucose metabolism-related markers in streptozotocin-damaged rat brain. J Neural Transm (Vienna) 2001; 108(12): 1457-74.
[http://dx.doi.org/10.1007/s007020100020] [PMID: 11810408]
[92]
Zhou L, Meng Q, Qian T, Yang Z. Ginkgo biloba extract enhances glucose tolerance in hyperinsulinism-induced hepatic cells. J Nat Med 2011; 65(1): 50-6.
[http://dx.doi.org/10.1007/s11418-010-0456-z] [PMID: 20814756]
[93]
Cong W-n, Tao R-y, Tian J-y, et al. EGb761, an extract of Ginkgo biloba leaves, reduces insulin resistance in a high-fat-fed mouse model. Acta Pharm Sin B 2011; 1: 14-20.
[http://dx.doi.org/10.1016/j.apsb.2011.04.006]
[94]
Kim S-C, Han M-Y, Kim H-J, Jung K-H. The effect of Ginkgo biloba Extract (GB) on Glucose Uptake in L6 Rat Skeletal Muscle Cells. Korea J Herbology 2007; 22: 155-61.
[95]
Auger C, Teissedre PL, Gérain P, et al. Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem 2005; 53(6): 2015-21.
[http://dx.doi.org/10.1021/jf048177q] [PMID: 15769129]
[96]
Liou CJ, Lai XY, Chen YL, Wang CL, Wei CH, Huang WC. Ginkgolide C suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signaling pathway. Evid Based Complement Alternat Med 2015; 2015 298635
[http://dx.doi.org/10.1155/2015/298635] [PMID: 26413119]
[97]
Huang WC, Chen YL, Liu HC, Wu SJ, Liou CJ. Ginkgolide C reduced oleic acid-induced lipid accumulation in HepG2 cells. Saudi Pharm J 2018; 26(8): 1178-84.
[http://dx.doi.org/10.1016/j.jsps.2018.07.006] [PMID: 30532639]
[98]
Perez-Vizcaino F, Duarte J, Jimenez R, Santos-Buelga C, Osuna A. Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 2009; 61(1): 67-75.
[http://dx.doi.org/10.1016/S1734-1140(09)70008-8] [PMID: 19307694]
[99]
Mansour SM, Bahgat AK, El-Khatib AS, Khayyal MT. Ginkgo biloba extract (EGb 761) normalizes hypertension in 2K, 1C hypertensive rats: role of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction. Phytomedicine 2011; 18(8-9): 641-7.
[http://dx.doi.org/10.1016/j.phymed.2011.01.014] [PMID: 21353510]
[100]
Abdel-Zaher AO, Farghaly HSM, El-Refaiy AEM, Abd-Eldayem AM. Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761) against hypertension-induced renal injury in rats. Clin Exp Hypertens 2018; 40(8): 703-14.
[http://dx.doi.org/10.1080/10641963.2018.1425421] [PMID: 29351002]
[101]
Brinkley TE, Lovato JF, Arnold AM, et al. Effect of Ginkgo biloba on blood pressure and incidence of hypertension in elderly men and women. Am J Hypertens 2010; 23(5): 528-33.
[http://dx.doi.org/10.1038/ajh.2010.14] [PMID: 20168306]
[102]
Arenz A, Klein M, Fiehe K, et al. Occurrence of neurotoxic 4′-O-methylpyridoxine in Ginkgo biloba leaves, Ginkgo medications and Japanese Ginkgo food. Planta Med 1996; 62(6): 548-51.
[http://dx.doi.org/10.1055/s-2006-957967] [PMID: 17252495]
[103]
Rider CV, Nyska A, Cora MC, et al. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets. Toxicol Pathol 2014; 42(5): 830-43.
[http://dx.doi.org/10.1177/0192623313501235] [PMID: 23960164]
[104]
Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009; 69(13): 1777-98.
[http://dx.doi.org/10.2165/11317010-000000000-00000] [PMID: 19719333]
[105]
Diamond BJ, Bailey MR. Ginkgo biloba: indications, mechanisms, and safety. Psychiatr Clin North Am 2013; 36(1): 73-83.
[http://dx.doi.org/10.1016/j.psc.2012.12.006] [PMID: 23538078]
[106]
Miwa H, Iijima M, Tanaka S, Mizuno Y. Generalized convulsions after consuming a large amount of gingko nuts. Epilepsia 2001; 42(2): 280-1.
[http://dx.doi.org/10.1046/j.1528-1157.2001.33100.x] [PMID: 11240603]
[107]
Hashiguchi M, Ohta Y, Shimizu M, Maruyama J, Mochizuki M. Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia. J Pharm Health Care Sci 2015; 1: 14.
[http://dx.doi.org/10.1186/s40780-015-0014-7] [PMID: 26819725]
[108]
Bonassi S, Prinzi G, Lamonaca P, et al. Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect®Plus) in elderly: a randomised placebo-controlled clinical trial [GiBiEx]. BMC Complement Altern Med 2018; 18(1): 22.
[http://dx.doi.org/10.1186/s12906-018-2080-5] [PMID: 29357859]
[109]
Ahmad MF. Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement. Biomed Pharmacother 2018; 107: 507-19.
[http://dx.doi.org/10.1016/j.biopha.2018.08.036] [PMID: 30114634]
[110]
Heleno SA, Barros L, Martins A, et al. Fruiting body, spores and in vitro produced mycelium of Ganoderma lucidum from Northeast Portugal: A comparative study of the antioxidant potential of phenolic and polysaccharidic extracts. Food Res Int 2012; 46: 135-40.
[http://dx.doi.org/10.1016/j.foodres.2011.12.009]
[111]
Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, Bisen PS. Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol 2009; 10(8): 717-42.
[http://dx.doi.org/10.2174/138920109789978757] [PMID: 19939212]
[112]
Wang J, Cao B, Zhao H, Feng J. Emerging roles of Ganoderma lucidum in anti-aging. Aging Dis 2017; 8(6): 691-707.
[http://dx.doi.org/10.14336/AD.2017.0410] [PMID: 29344411]
[113]
Sudheesh NP, Ajith TA, Janardhanan KK. Ganoderma lucidum (Fr.) P. Karst enhances activities of heart mitochondrial enzymes and respiratory chain complexes in the aged rat. Biogerontology 2009; 10(5): 627-36.
[http://dx.doi.org/10.1007/s10522-008-9208-9] [PMID: 19123066]
[114]
Hagen TM, Moreau R, Suh JH, Visioli F. Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Ann N Y Acad Sci 2002; 959: 491-507.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02119.x] [PMID: 11976222]
[115]
Sudheesh NP, Ajith TA, Ramnath V, Janardhanan KK. Therapeutic potential of Ganoderma lucidum (Fr.) P. Karst. against the declined antioxidant status in the mitochondria of post-mitotic tissues of aged mice. Clin Nutr 2010; 29(3): 406-12.
[http://dx.doi.org/10.1016/j.clnu.2009.12.003] [PMID: 20044182]
[116]
Mc Auley MT, Guimera AM, Hodgson D, et al. Modelling the molecular mechanisms of aging. Biosci Rep 2017; 37(1) BSR20160177
[http://dx.doi.org/10.1042/BSR20160177] [PMID: 28096317]
[117]
Lee JM, Kwon H, Jeong H, et al. Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res 2001; 15(3): 245-9.
[http://dx.doi.org/10.1002/ptr.830] [PMID: 11351361]
[118]
Shi YL, James AE, Benzie IF, Buswell JA. Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage to cellular DNA. Teratog Carcinog Mutagen 2002; 22(2): 103-11.
[http://dx.doi.org/10.1002/tcm.10008] [PMID: 11835288]
[119]
Longo VD, Kennedy BK. Sirtuins in aging and age-related disease. Cell 2006; 126(2): 257-68.
[http://dx.doi.org/10.1016/j.cell.2006.07.002] [PMID: 16873059]
[120]
Lapierre LR, Hansen M. Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol Metab 2012; 23(12): 637-44.
[http://dx.doi.org/10.1016/j.tem.2012.07.007] [PMID: 22939742]
[121]
Cuong VT, Chen W, Shi J, et al. The anti-oxidation and anti-aging effects of Ganoderma lucidum in Caenorhabditis elegans. Exp Gerontol 2019; 117: 99-105.
[http://dx.doi.org/10.1016/j.exger.2018.11.016] [PMID: 30476533]
[122]
Chuang MH, Chiou SH, Huang CH, Yang WB, Wong CH. The lifespan-promoting effect of acetic acid and Reishi polysaccharide. Bioorg Med Chem 2009; 17(22): 7831-40.
[http://dx.doi.org/10.1016/j.bmc.2009.09.002] [PMID: 19837596]
[123]
Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci 2016; 73(17): 3221-47.
[http://dx.doi.org/10.1007/s00018-016-2223-0] [PMID: 27100828]
[124]
Lee YH, Kim JH, Song CH, et al. Ethanol extract of Ganoderma lucidum augments cellular anti-oxidant defense through activation of Nrf2/HO-1. J Pharmacopuncture 2016; 19(1): 59-69.
[http://dx.doi.org/10.3831/KPI.2016.19.008] [PMID: 27280051]
[125]
Sass G, Soares MC, Yamashita K, et al. Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. Hepatology 2003; 38(4): 909-18.
[http://dx.doi.org/10.1002/hep.1840380417] [PMID: 14512878]
[126]
Balistreri CR. Anti-inflamm-ageing and/or anti-age-related disease emerging treatments: a historical alchemy or revolutionary effective procedures? Mediators Inflamm 2018; 2018 3705389
[http://dx.doi.org/10.1155/2018/3705389] [PMID: 29576745]
[127]
Ha T, Oh J, Khoi NM, et al. In vitro and in vivo hepatoprotective effect of ganodermanontriol against t-BHP-induced oxidative stress. J Ethnopharmacol 2013; 150(3): 875-85.
[http://dx.doi.org/10.1016/j.jep.2013.09.039] [PMID: 24140584]
[128]
Lee YJ, Jeong HY, Kim YB, et al. Reactive oxygen species and PI3K/Akt signaling play key roles in the induction of Nrf2-driven heme oxygenase-1 expression in sulforaphane-treated human mesothelioma MSTO-211H cells. Food Chem Toxicol 2012; 50(2): 116-23.
[http://dx.doi.org/10.1016/j.fct.2011.10.035] [PMID: 22019695]
[129]
Sid B, Verrax J, Calderon PB. Role of AMPK activation in oxidative cell damage: Implications for alcohol-induced liver disease. Biochem Pharmacol 2013; 86(2): 200-9.
[http://dx.doi.org/10.1016/j.bcp.2013.05.007] [PMID: 23688501]
[130]
Li B, Lee DS, Kang Y, Yao NQ, An RB, Kim YC. Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes. Food Chem Toxicol 2013; 53: 317-24.
[http://dx.doi.org/10.1016/j.fct.2012.12.016] [PMID: 23266269]
[131]
Wachtel-Galor S, Tomlinson B, Benzie IF. Ganoderma lucidum (“Lingzhi”), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study. Br J Nutr 2004; 91(2): 263-9.
[http://dx.doi.org/10.1079/BJN20041039] [PMID: 14756912]
[132]
Wachtel-Galor S, Wong W-c, Choi S-W, Benzie IFF. Antioxidant power and DNA repair effects of lingzhi or reishi medicinal mushroom, Ganoderma lucidum (Fr.) P. Karst. (Aphyllophoromycetideae), in human acute post-ingestion study. Int J Med Mushrooms 2010; 12: 359-66.
[http://dx.doi.org/10.1615/IntJMedMushr.v12.i4.30]
[133]
Deary IJ, Corley J, Gow AJ, et al. Age-associated cognitive decline. Br Med Bull 2009; 92: 135-52.
[http://dx.doi.org/10.1093/bmb/ldp033] [PMID: 19776035]
[134]
Wang M-F, Chan Y-C, Wu C-L, et al. Effects of ganoderma on aging and learning and memory ability in senescence accelerated mice. Int Congr Ser 2004; 1260: 399-404.
[http://dx.doi.org/10.1016/S0531-5131(03)01682-0]
[135]
Sun XZ, Liao Y, Li W, Guo LM. Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Neural Regen Res 2017; 12(6): 953-8.
[http://dx.doi.org/10.4103/1673-5374.208590] [PMID: 28761429]
[136]
Zhang R, Xu S, Cai Y, Zhou M, Zuo X, Chan P. Ganoderma lucidum protects dopaminergic neuron degeneration through inhibition of microglial activation. Evid Based Complement Alternat Med 2011; 2011 156810
[http://dx.doi.org/10.1093/ecam/nep075] [PMID: 19617199]
[137]
Lai CS, Yu MS, Yuen WH, So KF, Zee SY, Chang RC. Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum. Brain Res 2008; 1190: 215-24.
[http://dx.doi.org/10.1016/j.brainres.2007.10.103] [PMID: 18083148]
[138]
Chong YH, Shin YJ, Lee EO, Kayed R, Glabe CG, Tenner AJ. ERK1/2 activation mediates Abeta oligomer-induced neurotoxicity via caspase-3 activation and tau cleavage in rat organotypic hippocampal slice cultures. J Biol Chem 2006; 281(29): 20315-25.
[http://dx.doi.org/10.1074/jbc.M601016200] [PMID: 16714296]
[139]
Cheung WM, Hui WS, Chu PW, Chiu SW, Ip NY. Ganoderma extract activates MAP kinases and induces the neuronal differentiation of rat pheochromocytoma PC12 cells. FEBS Lett 2000; 486(3): 291-6.
[http://dx.doi.org/10.1016/S0014-5793(00)02317-6] [PMID: 11119721]
[140]
Sarwar N, Gao P, Seshasai SR, et al. Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375(9733): 2215-22.
[http://dx.doi.org/10.1016/S0140-6736(10)60484-9] [PMID: 20609967]
[141]
Chaudhury A, Duvoor C, Reddy Dendi VS, et al. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Front Endocrinol (Lausanne) 2017; 8: 6.
[http://dx.doi.org/10.3389/fendo.2017.00006] [PMID: 28167928]
[142]
Li F, Zhang Y, Zhong Z. Antihyperglycemic effect of ganoderma lucidum polysaccharides on streptozotocin-induced diabetic mice. Int J Mol Sci 2011; 12(9): 6135-45.
[http://dx.doi.org/10.3390/ijms12096135] [PMID: 22016649]
[143]
Seto SW, Lam TY, Tam HL, et al. Novel hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic (+db/+db) mice. Phytomedicine 2009; 16(5): 426-36.
[http://dx.doi.org/10.1016/j.phymed.2008.10.004] [PMID: 19109000]
[144]
Oda H, Okuda Y, Yoshida Y, Kimura N, Kakinuma A. Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats. Biochem Biophys Res Commun 2015; 466(3): 306-11.
[http://dx.doi.org/10.1016/j.bbrc.2015.09.010] [PMID: 26348778]
[145]
Xiao C, Wu QP, Cai W, Tan JB, Yang XB, Zhang JM. Hypoglycemic effects of Ganoderma lucidum polysaccharides in type 2 diabetic mice. Arch Pharm Res 2012; 35(10): 1793-801.
[http://dx.doi.org/10.1007/s12272-012-1012-z] [PMID: 23139131]
[146]
Xiao C, Wu Q, Zhang J, Xie Y, Cai W, Tan J. Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice. J Ethnopharmacol 2017; 196: 47-57.
[http://dx.doi.org/10.1016/j.jep.2016.11.044] [PMID: 27902927]
[147]
Zhang HN, Lin ZB. Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacol Sin 2004; 25(2): 191-5.
[PMID: 14769208]
[148]
Teng BS, Wang CD, Zhang D, et al. Hypoglycemic effect and mechanism of a proteoglycan from ganoderma lucidum on streptozotocin-induced type 2 diabetic rats. Eur Rev Med Pharmacol Sci 2012; 16(2): 166-75.
[PMID: 22428467]
[149]
Yang Z, Wu F, He Y, et al. A novel PTP1B inhibitor extracted from Ganoderma lucidum ameliorates insulin resistance by regulating IRS1-GLUT4 cascades in the insulin signaling pathway. Food Funct 2018; 9(1): 397-406.
[http://dx.doi.org/10.1039/C7FO01489A] [PMID: 29215104]
[150]
Gao Y, Lan J, Dai X, Ye J, Zhou S. A Phase I/II Study of Ling Zhi Mushroom Ganoderma lucidum (Fr.) Lloyd (Aphyllophoromycetideae) extract in patients with type II diabetes mellitus. Int J Med Mushrooms 2004; 6: 8.
[http://dx.doi.org/10.1615/IntJMedMushr.v6.i1.30]
[151]
Klupp NL, Kiat H, Bensoussan A, Steiner GZ, Chang DH. A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Sci Rep 2016; 6: 29540.
[http://dx.doi.org/10.1038/srep29540] [PMID: 27511742]
[152]
Miller M. Dyslipidemia and cardiovascular risk: the importance of early prevention. QJM 2009; 102(9): 657-67.
[http://dx.doi.org/10.1093/qjmed/hcp065] [PMID: 19498039]
[153]
Chen WQ, Luo SH, Ll HZ, Yang H. [Effects of ganoderma lucidum polysaccharides on serum lipids and lipoperoxidation in experimental hyperlipidemic rats]. Zhongguo Zhongyao Zazhi 2005; 30(17): 1358-60.
[PMID: 16323548]
[154]
Wang CD, Teng BS, He YM, et al. Effect of a novel proteoglycan PTP1B inhibitor from Ganoderma lucidum on the amelioration of hyperglycaemia and dyslipidaemia in db/db mice. Br J Nutr 2012; 108(11): 2014-25.
[http://dx.doi.org/10.1017/S0007114512000153] [PMID: 22453054]
[155]
Pan D, Zhang D, Wu J, et al. Antidiabetic, antihyperlipidemic and antioxidant activities of a novel proteoglycan from ganoderma lucidum fruiting bodies on db/db mice and the possible mechanism. PLoS One 2013; 8(7) e68332
[http://dx.doi.org/10.1371/journal.pone.0068332] [PMID: 23874589]
[156]
Chang CJ, Lin CS, Lu CC, et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun 2015; 6: 7489.
[http://dx.doi.org/10.1038/ncomms8489] [PMID: 26102296]
[157]
Liang Z, Yuan Z, Li G, Fu F, Shan Y. Hypolipidemic, antioxidant, and antiapoptotic effects of polysaccharides extracted from Reishi Mushroom, Ganoderma lucidum (Leysser: Fr) Karst, in mice fed a high-fat diet. J Med Food 2018; 21(12): 1218-27.
[http://dx.doi.org/10.1089/jmf.2018.4182] [PMID: 30183494]
[158]
Wang F, Zhou Z, Ren X, et al. Effect of Ganoderma lucidum spores intervention on glucose and lipid metabolism gene expression profiles in type 2 diabetic rats. Lipids Health Dis 2015; 14: 49.
[http://dx.doi.org/10.1186/s12944-015-0045-y] [PMID: 25994182]
[159]
Guo WL, Pan YY, Li L, Li TT, Liu B, Lv XC. Ethanol extract of Ganoderma lucidum ameliorates lipid metabolic disorders and modulates the gut microbiota composition in high-fat diet fed rats. Food Funct 2018; 9(6): 3419-31.
[http://dx.doi.org/10.1039/C8FO00836A] [PMID: 29877551]
[160]
Chu TT, Benzie IF, Lam CW, Fok BS, Lee KK, Tomlinson B. Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial. Br J Nutr 2012; 107(7): 1017-27.
[http://dx.doi.org/10.1017/S0007114511003795] [PMID: 21801467]
[161]
Zhang J, Gao X, Pan Y, Xu N, Jia L. Toxicology and immunology of Ganoderma lucidum polysaccharides in Kunming mice and Wistar rats. Int J Biol Macromol 2016; 85: 302-10.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.12.090] [PMID: 26763176]
[162]
Smina TP, Mathew J, Janardhanan KK, Devasagayam TP. Antioxidant activity and toxicity profile of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst occurring in South India. Environ Toxicol Pharmacol 2011; 32(3): 438-46.
[http://dx.doi.org/10.1016/j.etap.2011.08.011] [PMID: 22004964]
[163]
Wicks SM, Tong R, Wang CZ, et al. Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial. Am J Chin Med 2007; 35(3): 407-14.
[http://dx.doi.org/10.1142/S0192415X07004928] [PMID: 17597499]
[164]
Kwok Y, Ng KF, Li CC, Lam CC, Man RY. A prospective, randomized, double-blind, placebo-controlled study of the platelet and global hemostatic effects of Ganoderma lucidum (Ling-Zhi) in healthy volunteers. Anesth Analg 2005; 101(2): 423-6.
[http://dx.doi.org/10.1213/01.ANE.0000155286.20467.28] [PMID: 16037156]
[165]
Tao J, Feng KY. Experimental and clinical studies on inhibitory effect of ganoderma lucidum on platelet aggregation. J Tongji Med Univ 1990; 10(4): 240-3.
[http://dx.doi.org/10.1007/BF02887938] [PMID: 2098581]
[166]
Necyk C, Zubach-Cassano L. Natural health products and diabetes: A practical review. Can J Diabetes 2017; 41(6): 642-7.
[http://dx.doi.org/10.1016/j.jcjd.2017.06.014] [PMID: 28826695]
[167]
Fu J, Wang Z, Huang L, et al. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother Res 2014; 28(9): 1275-83.
[http://dx.doi.org/10.1002/ptr.5188] [PMID: 25087616]
[168]
Jin M, Zhao K, Huang Q, Shang P. Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol 2014; 64: 257-66.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.12.002] [PMID: 24325861]
[169]
Liu P, Zhao H, Luo Y. Anti-aging implications of Astragalus Membranaceus (Huangqi): A well-known Chinese tonic. Aging Dis 2017; 8(6): 868-86.
[http://dx.doi.org/10.14336/AD.2017.0816] [PMID: 29344421]
[170]
Lei H, Wang B, Li WP, Yang Y, Zhou AW, Chen MZ. Anti-aging effect of astragalosides and its mechanism of action. Acta Pharmacol Sin 2003; 24(3): 230-4.
[PMID: 12617771]
[171]
Xia G, Han X, Qi J, et al. The effects of Astragalus polysaccharide on zebrafish cell apoptosis and senescence. Am J Mol Biol 2012; 2: 103-9.
[http://dx.doi.org/10.4236/ajmb.2012.22011]
[172]
Zhang H, Pan N, Xiong S, et al. Inhibition of polyglutamine-mediated proteotoxicity by Astragalus membranaceus polysaccharide through the DAF-16/FOXO transcription factor in Caenorhabditis elegans. Biochem J 2012; 441(1): 417-24.
[http://dx.doi.org/10.1042/BJ20110621] [PMID: 21892924]
[173]
Salvador L, Singaravelu G, Harley CB, Flom P, Suram A, Raffaele JM. A natural product telomerase activator lengthens telomeres in humans: a randomized, double blind, and placebo controlled study. Rejuvenation Res 2016; 19(6): 478-84.
[http://dx.doi.org/10.1089/rej.2015.1793] [PMID: 26950204]
[174]
Huang YC, Tsay HJ, Lu MK, et al. Astragalus membranaceus-polysaccharides ameliorates obesity, hepatic steatosis, neuroinflammation and cognition impairment without affecting amyloid deposition in metabolically stressed APPswe/PS1dE9 mice. Int J Mol Sci 2017; 18(12) E2746
[http://dx.doi.org/10.3390/ijms18122746] [PMID: 29258283]
[175]
Cai H, Liang Q, Ge G. Gypenoside attenuates beta amyloid-induced inflammation in N9 microglial cells via SOCS1 signaling. Neural Plast 2016; 2016 6362707
[http://dx.doi.org/10.1155/2016/6362707] [PMID: 27213058]
[176]
Pan YF, Jia XT, Song EF, Peng XZ. Astragaloside protects against abeta1-42-induced oxidative stress, neuroinflammation and cognitive impairment in rats. Chin Med Sci J 2018; 33(1): 29-37.
[PMID: 29620512]
[177]
Li H, Shi R, Ding F, et al. Astragalus polysaccharide suppresses 6-hydroxydopamine-induced neurotoxicity in Caenorhabditis Elegans. Oxid Med Cell Longev 2016; 2016 4856761
[http://dx.doi.org/10.1155/2016/4856761] [PMID: 27885333]
[178]
Wang C, Li Y, Hao M, Li W. Astragaloside IV inhibits triglyceride accumulation in insulin-resistant HEPG2 cells via AMPK-induced srebp-1c phosphorylation. Front Pharmacol 2018; 9: 345.
[http://dx.doi.org/10.3389/fphar.2018.00345] [PMID: 29713279]
[179]
Jiang P, Ma D, Wang X, et al. Astragaloside IV prevents obesity-associated hypertension by improving pro-inflammatory reaction and leptin resistance. Mol Cells 2018; 41(3): 244-55.
[PMID: 29562733]
[180]
Song G, Han P, Sun H, et al. Astragaloside IV ameliorates early diabetic nephropathy by inhibition of MEK1/2-ERK1/2-RSK2 signaling in streptozotocin-induced diabetic mice. J Int Med Res 2018; 46(7): 2883-97.
[http://dx.doi.org/10.1177/0300060518778711] [PMID: 29896981]
[181]
Yuan LB, Hua CY, Gao S, et al. Astragalus polysaccharides attenuate monocrotaline-induced pulmonary arterial hypertension in rats. Am J Chin Med 2017; 45(4): 773-89.
[http://dx.doi.org/10.1142/S0192415X17500410] [PMID: 28521513]
[182]
Cheng Y, Tang K, Wu S, et al. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins. PLoS One 2011; 6(11) e27437
[http://dx.doi.org/10.1371/journal.pone.0027437] [PMID: 22110652]
[183]
Ke B, Ke X, Wan X, et al. Astragalus polysaccharides attenuates TNF-α-induced insulin resistance via suppression of miR-721 and activation of PPAR-γ and PI3K/AKT in 3T3-L1 adipocytes. Am J Transl Res 2017; 9(5): 2195-206.
[PMID: 28559971]
[184]
Jing LIU, Zhong-zhen Z, Hu-biao C. Review of Astragali radix. Chin Herb Med 2011; 3: 90-105.
[185]
Yuan YM, Gao JW, Shi Z, et al. Herb-drug pharmacokinetic interaction between radix astragali and pioglitazone in rats. J Ethnopharmacol 2012; 144(2): 300-4.
[http://dx.doi.org/10.1016/j.jep.2012.09.012] [PMID: 23026308]
[186]
Xie JH, Chen ZW, Pan YW, et al. Evaluation of safety of modified-Danggui Buxue Tang in rodents:immunological, toxicity and hormonal aspects. J Ethnopharmacol 2016; 183: 59-70.
[http://dx.doi.org/10.1016/j.jep.2015.12.049] [PMID: 26732632]
[187]
Mishra RN, Joshi D. Jiao Gu Lan (Gynostemma Pentaphyllum): The Chinese Rasayan-Current Jiao Gu Lan (Gynostemma Pentaphyllum): The Chinese Rasayan- current research scenario. Int J Res Pharma Biomed Sci 2011; 2: 1503-19.
[188]
Razmovski-Naumovski V, Huang TH-W, Tran VH, et al. Chemistry and pharmacology of Gynostemma Pentaphyllum. Phytochem Rev 2005; 4: 197-219.
[http://dx.doi.org/10.1007/s11101-005-3754-4]
[189]
Li L, Jiao L, Lau BH. Protective effect of gypenosides against oxidative stress in phagocytes, vascular endothelial cells and liver microsomes. Cancer Biother 1993; 8(3): 263-72.
[http://dx.doi.org/10.1089/cbr.1993.8.263] [PMID: 7804367]
[190]
Aktan F, Henness S, Roufogalis BD, Ammit AJ. Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression. Nitric Oxide 2003; 8(4): 235-42.
[http://dx.doi.org/10.1016/S1089-8603(03)00032-6] [PMID: 12895433]
[191]
Huang TH, Li Y, Razmovski-Naumovski V, et al. Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway. J Biomed Sci 2006; 13(4): 535-48.
[http://dx.doi.org/10.1007/s11373-006-9076-8] [PMID: 16525884]
[192]
Yang F, Shi H, Zhang X, Yang H, Zhou Q, Yu LL. Two new saponins from tetraploid jiaogulan (Gynostemma pentaphyllum), and their anti-inflammatory and α-glucosidase inhibitory activities. Food Chem 2013; 141(4): 3606-13.
[http://dx.doi.org/10.1016/j.foodchem.2013.06.015] [PMID: 23993527]
[193]
Wong WY, Lee MM, Chan BD, et al. Gynostemma pentaphyllum saponins attenuate inflammation in vitro and in vivo by inhibition of NF-κB and STAT3 signaling. Oncotarget 2017; 8(50): 87401-14.
[http://dx.doi.org/10.18632/oncotarget.20997] [PMID: 29152090]
[194]
Shen CY, Jiang JG, Shi MM, Yang HL, Wei H, Zhu W. Comparison of the effects and inhibitory pathways of the constituents from Gynostemma Pentaphyllum against lps-induced inflammatory response. J Agric Food Chem 2018; 66(43): 11337-46.
[http://dx.doi.org/10.1021/acs.jafc.8b03903] [PMID: 30301351]
[195]
Keilhoff G, Esser T, Titze M, Ebmeyer U, Schild L. Gynostemma pentaphyllum is neuroprotective in a rat model of cardiopulmonary resuscitation. Exp Ther Med 2017; 14(6): 6034-46.
[PMID: 29250141]
[196]
Kim KS, Zhao TT, Shin KS, et al. Gynostemma Pentaphyllum ethanolic extract protects against memory deficits in an MPTP-lesioned mouse model of Parkinson’s disease treated with L-DOPA. J Med Food 2017; 20(1): 11-8.
[http://dx.doi.org/10.1089/jmf.2016.3764] [PMID: 28005447]
[197]
Lin-Na S, Yong-Xiu S. Effects of polysaccharides from Gynostemma pentaphyllum (Thunb.), Makino on physical fatigue. Afr J Tradit Complement Altern Med 2014; 11(3): 112-7.
[http://dx.doi.org/10.4314/ajtcam.v11i3.17] [PMID: 25371572]
[198]
Choi HS, Zhao TT, Shin KS, et al. Anxiolytic effects of herbal ethanol extract from Gynostemma pentaphyllum in mice after exposure to chronic stress. Molecules 2013; 18(4): 4342-56.
[http://dx.doi.org/10.3390/molecules18044342] [PMID: 23584055]
[199]
Megalli S, Aktan F, Davies NM, Roufogalis BD. Phytopreventative anti-hyperlipidemic effects of gynostemma pentaphyllum in rats. J Pharm Pharm Sci 2005; 8(3): 507-15.
[PMID: 16401396]
[200]
Wang M, Wang F, Wang Y, Ma X, Zhao M, Zhao C. Metabonomics study of the therapeutic mechanism of Gynostemma pentaphyllum and atorvastatin for hyperlipidemia in rats. PLoS One 2013; 8(11) e78731
[http://dx.doi.org/10.1371/journal.pone.0078731] [PMID: 24223845]
[201]
Gauhar R, Hwang SL, Jeong SS, et al. Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol Lett 2012; 34(9): 1607-16.
[http://dx.doi.org/10.1007/s10529-012-0944-1] [PMID: 22576281]
[202]
Park SH, Huh TL, Kim SY, et al. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial. Obesity (Silver Spring) 2014; 22(1): 63-71.
[http://dx.doi.org/10.1002/oby.20539] [PMID: 23804546]
[203]
Megalli S, Davies NM, Roufogalis BD. Anti-hyperlipidemic and hypoglycemic effects of Gynostemma pentaphyllum in the Zucker fatty rat. J Pharm Pharm Sci 2006; 9(3): 281-91.
[PMID: 17207412]
[204]
Lokman EF, Gu HF, Wan Mohamud WN, Östenson CG. Evaluation of antidiabetic effects of the traditional medicinal plant Gynostemma Pentaphyllum and the possible mechanisms of insulin release. Evid Based Complement Alternat Med 2015; 2015 120572
[http://dx.doi.org/10.1155/2015/120572] [PMID: 26199630]
[205]
Wang Z, Zhao X, Liu X, et al. Anti-diabetic activity evaluation of a polysaccharide extracted from Gynostemma pentaphyllum. Int J Biol Macromol 2019; 126: 209-14.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.12.231] [PMID: 30590141]
[206]
Norberg A, Hoa NK, Liepinsh E, et al. A novel insulin-releasing substance, phanoside, from the plant Gynostemma pentaphyllum. J Biol Chem 2004; 279(40): 41361-7.
[http://dx.doi.org/10.1074/jbc.M403435200] [PMID: 15220351]
[207]
Hoa NK, Norberg A, Sillard R, et al. The possible mechanisms by which phanoside stimulates insulin secretion from rat islets. J Endocrinol 2007; 192(2): 389-94.
[http://dx.doi.org/10.1677/joe.1.06948] [PMID: 17283239]
[208]
Gao D, Zhao M, Qi X, et al. Hypoglycemic effect of Gynostemma pentaphyllum saponins by enhancing the Nrf2 signaling pathway in STZ-inducing diabetic rats. Arch Pharm Res 2016; 39(2): 221-30.
[http://dx.doi.org/10.1007/s12272-014-0441-2] [PMID: 25066072]
[209]
Lundqvist LCE, Rattigan D, Ehtesham E, Demmou C, Östenson CG, Sandström C. Profiling and activity screening of Dammarane-type triterpen saponins from Gynostemma pentaphyllum with glucose-dependent insulin secretory activity. Sci Rep 2019; 9(1): 627.
[http://dx.doi.org/10.1038/s41598-018-37517-3] [PMID: 30679754]
[210]
Yeo J, Kang YJ, Jeon SM, et al. Potential hypoglycemic effect of an ethanol extract of Gynostemma pentaphyllum in C57BL/KsJ-db/db mice. J Med Food 2008; 11(4): 709-16.
[http://dx.doi.org/10.1089/jmf.2007.0148] [PMID: 19053864]
[211]
Yassin K, Huyen VT, Hoa KN, Ostenson CG. Herbal extract of gynostemma pentaphyllum decreases hepatic glucose output in type 2 diabetic goto-kakizaki rats. Int J Biomed Sci 2011; 7(2): 131-6.
[PMID: 23675229]
[212]
Huyen VT, Phan DV, Thang P, Hoa NK, Ostenson CG. Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients. Horm Metab Res 2010; 42(5): 353-7.
[http://dx.doi.org/10.1055/s-0030-1248298] [PMID: 20213586]
[213]
Huyen VT, Phan DV, Thang P, Hoa NK, Ostenson CG. Gynostemma Pentaphyllum tea Improves Insulin sensitivity in Type 2 diabetic patients. J Nutr Metab 2013; 2013 765383
[http://dx.doi.org/10.1155/2013/765383] [PMID: 23431428]
[214]
Attawish A, Chivapat S, Phadungpat S, et al. Chronic toxicity of Gynostemma pentaphyllum. Fitoterapia 2004; 75(6): 539-51.
[http://dx.doi.org/10.1016/j.fitote.2004.04.010] [PMID: 15351107]
[215]
Chiranthanut N, Teekachunhatean S, Panthong A, Khonsung P, Kanjanapothi D, Lertprasertsuk N. Toxicity evaluation of standardized extract of Gynostemma pentaphyllum Makino. J Ethnopharmacol 2013; 149(1): 228-34.
[http://dx.doi.org/10.1016/j.jep.2013.06.027] [PMID: 23796877]
[216]
Choi EK, Won YH, Kim SY, et al. Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 2019; 52: 198-205.
[http://dx.doi.org/10.1016/j.phymed.2018.05.002] [PMID: 30599899]
[217]
Wan ZH, Zhao Q. Gypenoside inhibits interleukin-1β-induced inflammatory response in human osteoarthritis chondrocytes. J Biochem Mol Toxicol 2017; 31(9) e21926
[http://dx.doi.org/10.1002/jbt.21926] [PMID: 28422402]
[218]
Al Disi SS, Anwar MA, Eid AH. Anti-hypertensive herbs and their mechanisms of action: part I. Front Pharmacol 2016; 6: 323.
[http://dx.doi.org/10.3389/fphar.2015.00323] [PMID: 26834637]
[219]
Posadino AM, Cossu A, Giordo R, et al. Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death. Food Chem Toxicol 2015; 78: 10-6.
[http://dx.doi.org/10.1016/j.fct.2015.01.017] [PMID: 25656643]
[220]
Posadino AM, Cossu A, Giordo R, et al. Coumaric acid induces mitochondrial damage and oxidative-mediated cell death of human endothelial cells. Cardiovasc Toxicol 2013; 13(3): 301-6.
[http://dx.doi.org/10.1007/s12012-013-9205-3] [PMID: 23504614]
[221]
Giordo R, Cossu A, Pasciu V, Hoa PT, Posadino AM, Pintus G. Different redox response elicited by naturally occurring antioxidants in human endothelial cells. Open Biochem J 2013; 7: 44-53.
[http://dx.doi.org/10.2174/1874091X01307010044] [PMID: 23730364]
[222]
Pasciu V, Posadino AM, Cossu A, et al. Akt downregulation by flavin oxidase-induced ROS generation mediates dose-dependent endothelial cell damage elicited by natural antioxidants. Toxicol Sci 2010; 114(1): 101-12.
[http://dx.doi.org/10.1093/toxsci/kfp301] [PMID: 20015842]


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