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Aging and disease    2017, Vol. 8 Issue (6) : 740-759     DOI: 10.14336/AD.2017.0720
Review |
Herba Cistanches: Anti-aging
Wang Ningqun1, Ji Shaozhen2, Zhang Hao3, Mei Shanshan2, Qiao Lumin4, Jin Xianglan5,*
1Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
3Department of Radiology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
4Department of Emergency, Traditional Chinese Medicine Hospital of Yinchuan, Ningxia Hui Nationality Autonomous Region 750001, China.
5Department of Neurology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China.
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Abstract  

The Cistanche species (“Rou Cong Rong” in Chinese) is an endangered wild species growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been used as a tonic in China for many years. Modern pharmacological studies have since demonstrated that Herba Cistanches possesses broad medicinal functions, especially for use in anti-senescence, anti-oxidation, neuroprotection, anti-inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti-osteoporosis and the promotion of bone formation. This review summarizes the up-to-date and comprehensive information on Herba Cistanches covering the aspects of the botany, traditional uses, phytochemistry and pharmacology, to lay ground for fully elucidating the potential mechanisms of Herba Cistanches’ anti-aging effect and promote its clinical application as an anti-aging herbal medicine.

Keywords Herba Cistanches      anti-senescence      anti-oxidation      neuroprotection     
Corresponding Authors: Jin Xianglan   
About author:

These authors contributed equally to this study

Issue Date: 01 December 2017
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Wang Ningqun
Ji Shaozhen
Zhang Hao
Mei Shanshan
Qiao Lumin
Jin Xianglan
Cite this article:   
Wang Ningqun,Ji Shaozhen,Zhang Hao, et al. Herba Cistanches: Anti-aging[J]. Aging and disease, 2017, 8(6): 740-759.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.0720     OR     http://www.aginganddisease.org/EN/Y2017/V8/I6/740
ExtractsFunctionMechanismsRefs.
Ethanol extract of Herba CistanchesLifespan elongationantagonize immunosenescence, exhibit analgesic and anti-inflammatory properties, improve blood circulation, increase the weights of the seminal vesicle, prostate gland and testes, modulate serum hormone level, induct testicular steroidogenic enzymes, delay accumulation of lactic acid, improve energy storage[23-31,36]
Cardioprotectionreduce oxidative stress, inhibit apoptotic pathways,
enhance mitochondrial ATP-GC and confer cardioprotection against ischemia/reperfusion (I/R) injury
[32,34]
Neuroprotectionincrease neuronal cell differentiation, neurite length, and synapse formation, upregulate NGF[33]
Aqueous extract of Herba CistanchesLifespan elongationinhibit cell apoptosis[38]
Antioxidant activityinhibit activation of macrophage cells and nitric oxide production, scavenge free radicals[37,39]
Hepatoprotectioninhibit lipid peroxidation in liver microsomes[39]
Anti-neoplastic effectupregulate nitric oxide synthase II expression, stimulate phagocytosis[40]
Memory and learning enhancementblock Aβ 1-42 amyloid deposition[41]
Anti-osteoporosis effectregulate bone metabolism related genes e.g., Smad1, Smad5, TGF-β1 and TIEG1[42-44]
Aphrodisiac effectalleviate spermatogenetic cell degeneration, modulate serum sex hormones levels[45-46]
Methanol extract of Herba CistanchesCardioprotectionenhance mitochondrial glutathione status, decrease mitochondrial Ca2+ level, decrease myocardial ATP depletion, mitochondrial membrane potential and respiration rate[47-48]
Vasorelaxant activityinhibit contractions induced by noradrenaline[49]
Hepatoprotectioninhibit D-GalN-induced death of hepatocytes, reduce TNF-α-induced cytotoxicity in L929 cells[49]
Table 1  The functions and mechanisms of Herba Cistanches extracts with anti-aging or anti-aging related effects.
Figure 1.  The chemical structures of PhGs

(A) Chemical structure of compounds 1-26 in PhGs. (B) Chemical structure of compound 27 (Crenatoside) in PhGs. (C) Chemical structure of compound 28 (Cistanoside F) in PhGs.

Active ingredientR1aR2aR3aR4aR5aR6aR7aSpeciesbRefs.
2'-Acetylacteoside (1)AcRhaCfHOHOHHCd, Ct[39, 50, 51]
Acteoside (2)HRhaCfHOHOHHCd, Ct[39, 50, 51]
Cistanoside A (3)HRhaCfGlcOmeOHHCd, Ct[39]
Cistanoside B (4)HRhaFrGlcOmeOHHCd[52]
Cistanoside C (5)HRhaCfHOmeOHHCd[52]
Cistanoside D (6)HRhaFrHOmeOHHCd[52]
Cistanoside E (7)HRhaHHOmeOHHCd[52]
Cistanoside G (8)HRhaHHHOHHCd[48]
Cistanoside H (9)AcRhaHHOHOHHCd[2]
Decaffeoylacteoside (10)HRhaHHOHOHHCd, Ct[49]
Echinacoside (11)HRhaCfGlcOHOHHCd, Ct[39, 48]
Isoacteoside (12)HRhaHCfOHOHHCd, Ct[39, 50, 51]
Isosyringalide-3'-α-L-rhamnopyranoside (13)HRhaCmHOHOHHCt[2]
Osmanthuside (14)HRhaCmHHOHHCd[53]
Salidroside (15)HHHHHOHHCd, Ct[49, 54]
Syringalide A-3'-α-L-rhamnopyranoside (16)HRhaCfHHOHHCd, Ct[39,51]
Tubuloside A (17)AcRhaCfGlcOHOHHCd, Ct[50]
Tubuloside B (18)AcRhaHCfOHOHHCd, Ct[39, 50]
Tubuloside C (19)AcTA-RhaCfGlcOHOHHCt[2]
Tubuloside D (20)AcTA-RhaCmGlcOHOHHCt[2]
Tubuloside E (21)AcTA-RhaCmHOHOHHCt[2]
Cistantubuloside A (22)HRhaCfGlcHOHHCt[49]
Cistantubuloside B1/B2(23)HRhaCm/c-CmGlcOHOHHCt[49]
Kankanoside F (24)HRhaHGlcOHOHHCt[48]
Kankanoside G (25)HRhaHCfHOHHCt[48]
Cistantubuloside C1/C2 (26)HRhaCfGlcOHOHOH(S/R)Ct[55]
Crenatoside (27)Ct[2]
Cistanoside F (28)Ct[39, 48, 49]
Table 2  Phenylethanoid glycosides from Herba Cistanche.
FunctionMechanismRefs.
Lifespan extensioninduce cell cycle arrest and apoptosis via induction of oxidative DNA damage[58,59,64,65,68]
modulate nuclear localization and transcriptional activities of daf-16
prevent decrease in membrane potential of fragmented mitochondria
increase expression of the anti-apoptotic protein Bcl-2 and inhibiting caspase-3 activity
stimulate intestinal epithelial cell proliferation and prevent cell death via up-regulation of TGF-β
Memory and learning enhancementdecrease P-tau phosphorylation and increase CRMP-2 expression level[72]
Antioxidant effectimprove anti-oxidant enzymes[39,65,74-77]
inhibit formation of NO
clear all free radicals, scavenge DPPH and OH free radicals
protect oxidative stress-induced organ injuries by entering cells through the injured membrane, affecting the signaling pathway between ROS and the opening of Ca2+ channel
Neuroprotection effectreduce the levels of T-tau, TNF-α, and IL-1β[78-80]
inhibit cytochrome c release and caspase-3 activation via activating ERK pathway in neuronal cells
inhibit glutamate release by reducing voltage-dependent Ca2+ entry and suppressing protein kinase C activity
Anti-inflammationblock TNF-α-NO and COX-II-PGE2 pathways[37,74,82,83]
scavenge NO radical
upregulate TGF-β1 and increase the number of Ki67(+) proliferating cells in diseased colons
Anti-neurodegenerative effectincrease expression of GDNF and BDNF mRNA and protein, induce NTFs, inhibit apoptosis[85]
Immunomodulatory and anti-neoplastic effectsincrease intracellular oxidized guanine, 8-oxoG, and upregulate double-strand DNA break (DSB)-binding protein 53BP[87,88]
increase caspase 3 and cleaved PARP, upregulate G1/S-CDK blocker CDKN1B (p21) via induction of oxidative DNA damage
Hepatoprotective effectinhibit both ascorbic acid/Fe2+ and ADP/NADPH/Fe3+ induced lipid peroxidation[39,49,77,88-90]
reduce TNF-α-induced cytotoxicity
anti-hepatic fibrosis by reducing mRNA expression of NF-κB
inhibit hepatic stellate cell (HSC) activation, block conduction of TGF-β1/smad signaling pathways
decrease HBV replication and antigen expression
Anti-osteoporosis effectstimulate osteoblastic bone formation by promoting bone regeneration in cultured osteoblastic MC3T3-E1 cells[93-96]
increase cell proliferation, ALP activity, COL I contents, OCN levels and mineralization in osteoblasts, elevate OPG/RANKL ratio and decrease receptor activator of nuclear factor-kB ligand (RANKL) level in serum
promote differentiation of bone marrow mesenchymal stem cells cultured in vitro by increasing ZHX3 expression
Aphrodisiac effectincrease sperm count and sperm motility and attenuate poor sperm quality and testicular toxicity in rats by up-regulating steroidogenesis enzymes including StAR, CYP11A1, 3β-HSD, 17β-HSD, CYP17A1 and CYP3A4[31,98]
Anti-diabetic and anti-fatigue effectssuppress elevated fasting blood glucose and postprandial blood glucose levels, insulin resistance and dyslipidemia[36,99,100]
inhibit aldose reductase
enhance swimming capacity of mice by decreasing muscle damage, delay accumulation of lactic acid, and improve energy storage
Table 3  The function and mechanisms of echinacoside with anti-aging and anti-aging related effects.
FunctionMechanismRefs.
Lifespan extensioninhibit hepatic apoptosis[49,101,102]
Memory and learning enhancementpromote NGF and its neuronal actions, increase TrK A expression, upregulate NGF[33,103-105]
inhibit acetylcholine esterase and increase the activities of antioxidant enzymes
increase activity of GSH-Px, T-SOD, TChE and protein contents, and decrease MDA content
increase neurons and nissl bodies in the hippocampus, promote NGF and TrkA expression, decrease the content of nitric oxide, activity of nitric oxide synthase and expression of caspase-3 protein
Antioxidant effectscavenge NO radical and DPPH radical[38,65,103,106,107]
decrease activity of nitric oxide synthase
inhibit both ascorbic acid/Fe2+ and ADP/NADPH/Fe3+ induced lipid peroxidation in rat liver microsomes
Neuroprotective effectincrease neurons and nissl bodies in the hippocampus[41,103,104,108,109]
inhibit rotenone-induced α-synuclein, caspase-3 upregulation and MAP-2 downregulation
block amyloid deposition, reverse cholinergic and hippocampal dopaminergic neuronal function
improve SK-N-SH cell morphology, enhance cell survival rate, decrease cell LDH release rate and expression of phosphorylated tau proteins at p-Ser 199/202 and p-Ser 404 sites, up-regulate the expression of non-phosphorylated tau proteins at Ser 202 site and Ser 404 sites
Anti-inflammatory effectscavenge NO radical[74]
Immunomodulatory and anti-neoplastic effectsinhibit basophilic cell-derived immediate-type and delayed-type allergic reactions[110,111]
down-regulate expressions of the CCL1, CCL2, CCL3, CCL4, FCER1A and NFATC1 genes, inhibit MAPK pathway, and decrease JNK phosphorylation
Hepatoprotective effectantioxidative, immunoregulatory, regulate hepatic apoptosis[49,50,90,96,102]
inhibit TNF-α-mediated hepatic apoptosis and subsequent necrosis in DGalN/LPS-induced liver failure
scavenge free radicals, inhibit lipid peroxidation, protect hepatic membranes
block the TGF-β1/smad signaling pathway and inhibit the activation of HSC
inhibit D-GalN-induced death of hepatocytes and reduce TNF-α-induced cytotoxicity in L929 cells
block P450-mediated bioactivation
Anti- hypercholesterolemia and anti-diabetic effectsenhance mRNA expressions of apolipoprotein B, VLDL receptor, and cytochrome P450 SCC in HepG2 hepatocytes, in diet-induced hypercholesterolemia mice[25,36]
improve glucose tolerance in starch-loaded mice
Table 4  The functions and mechanisms of acteoside with anti-aging and anti-aging related effects.
FunctionMechanismRefs.
Antioxidant effectscavenge free radical such as NO radical[39,74,83]
Hepatoprotective effectinhibit both ascorbic acid/Fe2+ and ADP/NADPH/Fe3+ induced lipid peroxidation in rat liver microsomes[39,49]
reduce TNF-α-induced cytotoxicity
Neuroprotective effectinhibit microglia-involved neuroinflammation[83]
Table 5  The function and mechanisms of isoacteoside with anti-aging related effects.
FunctionActive ingredientMechanismRefs.
Immunological activityACDP-2stimulate immune response[114]
Cistanche
Deserticola polysaccharide (CDPS)
stimulate the division of thymus lymphocyte, promote thymus intracellular calcium delivering[113]
CDA-1Astimulate B cell proliferation[117]
CDA-3Bstimulate both T and B cell proliferation[117]
Hepatoprotective effectCDP-Cantioxidant, promote viability of HepG2 cells,
attenuate microvesicular steatosis and mild necrosis, reduce the contents of MDA and TG
[116]
Antioxidant activityCistanche tubulosa polysaccharide (CTP)scavenge DPPH, OH and ABTS radical[115]
Anti-diabetic effectCistanche tubulosa polysaccharide (CTP)suppress elevated fasting blood glucose and postprandial blood glucose levels, insulin resistance and dyslipidemia
suppress body weight loss in db/db mice
[99]
Table 6  Active ingredients, functions and mechanisms of Polysaccharides from Herba Cistanches with anti-aging related effects.
Active ingredientFunctionMechanismRefs.
Ethanol extract of Cistanche SalsaAnti-osteoporosis effectsuppress bone weight loss[118]
Anti-proliferative
effect
decrease prostate weight, serum dihydrotestosterone concentration, and mRNA expression of 5α-reductase type 1 and type 2, regulate the expression levels of inflammatory-related proteins and apoptosis-associated proteins[119]
Phenylethanoid
glycosides (PhGs)
Neuroprotective effectprevent cell apoptosis, protect dopaminergic neurons against dopamine neurotoxicity induced by MPTP[120-121]
EchinacosideLifespan extensionprotect cells from DNA damage, trigger cells in the G1 phase to enter the S phase and G2 phase, improve ROS degradation[122-124]
protect neuronal cells from apoptosis
maintain mitochondrial function, decrease the generation of ROS, increase the expression of the antiapoptotic protein Bcl-2 and inhibit caspase-3 activity
Anti-inflammatory
effect
reduce inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines[126]
Neuroprotective effectinhibit caspase-3 and caspase-8 activation in cerebellar granule neurons[127-130]
reduce ROS production, attenuate neurotoxicity mitochondrial dysfunction and inflammatory responses induced by 6-OHDA
suppress expression of apoptotic genes
inhibit generation of MPP+-induced ROS
decrease striatal extracellular levels of DA, DOPAC and HVA
Anti-neurodegenerative effectattenuate neurotoxicity mitochondrial dysfunction and inflammatory responses[123,125,127-128]
suppress dopaminergic neuron loss caused by MPP+ or MPTP
maintain dopamine content and dopamine metabolite content
increase striatal dopamine and dopamine metabolite levels
inhibit apoptosis and activation of microglia and astrocytes in the substantia nigra
regulate cytokines such as p38 MAPK and NF-κB p52 subunit
Anti-oxidant effectdecrease generation of ROS and protect oxidative-stress-induced toxic injuries[124]
Anti-neoplastic effectinhibit prostate cancer cell proliferation[132,133]
modulate MAPK activity
ActeosideSkin-protective effectenhance scavenging activity of ROS, decrease Bax/Bcl-2 ratio and downregulate activity of pro caspase-3[135]
modulate the MAPK signaling pathway
Neuroprotective effectinhibit neuronal death induced by MPP+ and glutamate[134]
Tubuloside BNeuroprotective effectinhibit cell apoptosis, attenuate MPP+ induced cytotoxicity, DNA fragmentation, and intracellular accumulation of ROS, anti-oxidative stress effects, maintenance of mitochondria function, decrease of concentration of free intracellular calcium, inhibition of caspase-3 activity[136,137]
(2E,6R)-8-Hydroxy-2,6-dimethyl-2-octenoic acid [(R)-HDOA]Anti-osteoporosis effectdecrease bone weight and mechanical strength[133]
Table 7  Active ingredients, functions and mechanisms of Cistanche Salsa with anti-aging and anti-aging related effects.
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