Natural Product Therapies in Chronic Kidney Diseases

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Yue Qiu^a, Yang Qiu^a, Guang-Min Yao^b, Changqing Luo^a, **, Chun Zhang^a,* et al

Abstract:

Ntevraumkab mobyog ib qho ntawm cov teeb meem kev noj qab haus huv thoob ntiaj teb. Cov tshuaj suav tshuaj tau siv dav raumob ntev raumkab mobkev kho mob. Nrog rau kev txhim kho cov cuab yeej phytochemistry niaj hnub no, cov khoom ntuj tsim tau raug cais tawm los ntawm cov tshuaj suav tshuaj, uas muab cov txheej txheem meej dua rau kev tshawb xyuas cov tshuaj suav tshuaj. Hauv tsab xov xwm no, peb tau xaiv yim yam khoom siv ntuj tsim los ntawm cov tshuaj suav tshuaj suav tshuaj rau kev kho mob raum mob raum los piav txog cov kev nce qib tsis ntev los no hauv kev txhim kho cov tshuaj tshiab.

Ntsiab lus:Ntevraumkab mobnatural khoom tshuaj suav tshuaj

cistanche tubolosa cov txiaj ntsig: kho mob raum kab mob

1. Taw qhia

Ntevraumkab mob(CKD) yog ib qho teeb meem kev noj qab haus huv thoob ntiaj teb nrog kev pom tsis zoo thiab muaj kev cuam tshuam tsawg. 10 feem pua ntawm cov pej xeem thoob ntiaj teb raug cuam tshuam los ntawm CKD nrog kev tuag siab [1]. Hauv 2012, 1.5 feem pua ntawm cov neeg tuag thoob ntiaj teb raug ntaus nqi rau CKD [2]. Cov tshuaj tseem ceeb rau CKD yog renin-angiotensin system (RAS) blockers, steroids, thiabtiv thaiv kab mobsuppressants. Txawm li cas los xij, qhov txiaj ntsig zoo ntawm RAS blockers raug txwv [3]. Meanwhile, cov kev mob tshwm sim ntawm steroids thiabtiv thaiv kab mobsuppressants yog, nrog rau kev kis kab mob thiab mob qog noj ntshav [4]. Yog li ntawd, cov tshuaj siv tau zoo rau CKD uas muaj kev phiv tsawg dua yog qhov xav tau sai.

Cov tshuaj suav tshuaj (TCMs) tau siv los kho ntau yam kab mob rau ntau tshaj 2,000 xyoo. Hauv Suav teb thiab lwm lub tebchaws Esxias, TCMs tau raug xaiv los ua lwm txoj kev kho mob rau CKD. Lub hauv paus ntsiab lus ntawm TCMs daim ntawv thov yog tswj hwm Yin thiab Yang qhov sib npaug hauv tag nrho lub cev [5]. TCMs feem ntau yog ua raws li cov kev paub dhau los uas tau sau tseg thiab kev sib koom ua ke ntawm cov tshuaj cog ntoo sib txawv. Kev qhia txog cov tshuaj suav tshuaj hauv Fab Kis tuaj yeem rov qab mus rau xyoo 1920 thaum acupuncture tau coj mus rau Fabkis cov kws kho mob [6]. Thiab qee qhov botany, uas tau siv rau hauv cov tshuaj suav tshuaj, kuj tau siv rau hauv Fabkis rau keeb kwm ntev, xws li Crataegus pinnatifid [7]. Txog rau xyoo 2006, muaj ntau dua 18,000 Cov chaw kho mob suav hauv Tebchaws Europe, thiab cov teebmeem kev kho mob ntawm cov tshuaj suav tshuaj tau paub ntau ntxiv [8,9].

Niaj hnub nimno pharmacology pab txhawb rau kev nce qib ntawm TCMs nyob rau hauv cov nqe lus ntawm kev sib cais thiab tshuaj xyuas cov tshuaj nquag. Nws tau tshaj tawm tias TCM hais txog niaj hnub kws tshuaj tau ua tiav pab cais cov tshuaj tiv thaiv kabmob malaria artemisinin (qinghaosu) los ntawm Artemisia annua, uas yog li no tau txais txiaj ntsig Nobel nqi zog hauv Physiology lossis Tshuaj hauv 2015. Tsis tas li ntawd, nws tau cawm ntau lab tus tib neeg thoob plaws ntiaj teb. mus txog 2015 [10]. Rau lwm qhov piv txwv, triptolide los ntawm Tripterygium Hook F tau pom zoo kom muaj kev tiv thaiv podocyte hauv cov qauv tsiaj ntawm membranous nephropathy [11]. Txoj kev loj hlob ntawm cov khoom ntuj tsim kom muaj qhov tseeb dua rau TCMs.

Qhov kev tshuaj xyuas no qhia txog rau rau feem ntau siv tshuaj ntsuab rau kev kho mob raum hauv Suav teb, kev ua tau zoo thiab cov txheej txheem ntawm yim cov khoom xyaw tseem ceeb cais tawm ntawm lawv, nrog rau cov kev hloov tshiab tshaj plaws hauv CKD txoj kev kho (Table 1).

cistanche stem

cistanche qia

2. Cov tshuaj thiab lawv cov tshuaj sib xws

2.1. Triptolide thiab celastrol

Tripterygium Hook F (TwHF), hu ua Lei Gong Teng (Thunder God Vine), tau siv rau kev mob caj dab thiab mob caj dab.CKDkev kho mob txij li xyoo 1970 hauv Suav teb [12,13]. Feem ntau cov ntawv tshaj tawm txog kev kho mob ntawm TwHF hauv kev kho mob raum yog nyob rau hauv cov ntawv xov xwm hauv cheeb tsam. Bin et al. ua ib qho kev soj ntsuam ntawm cov kev sim tshuaj ntsuam xyuas hauv Suav teb ntawm kev siv Tripterygium npaj (Tripterygium glycoside ntsiav tshuaj, Tripterygium Hutch ntsiav tshuaj, thiab Tripterygium granules lossis extracts) rau CKD kho [14]. Kuj tseem tau luam tawm cov kev sim tshuaj ua lus Askiv. Yongchun et al. tau tshaj tawm tias TwHF extract tuaj yeem txo cov proteinuria hauv cov neeg mob ntshav qab zib nephropathy nyob rau hauv ib qho kev sim randomized soj ntsuam [15].

TwHF muaj ntau yam khoom ntuj tsim, cov khoom xyaw tseem ceeb thiab muaj txiaj ntsig nrog rau triptolide thiab cestrol (CLT) nrog lub zog.tiv thaiv-mobthiabimmunosuppressivekev ua haujlwm[16]

2.1.1. Triptolide

Triptolide yog diterpenoid epoxide, muaj zog tiv thaiv kev ua haujlwm. Kev tshawb fawb hauv vitro tau pom tias triptolide cuam tshuam ntau yam ntawm peb qhov tseem ceeb pro-inflammatory genes ntxias los ntawm lipopolysaccharide (LPS) hauv nas RAW 264.7 macrophages: cyclooxygenase-2 (COX-2) (IC50=0.03 mM ), inducible nitric oxide synthase (iNOS) (IC50=0.04 mM), thiab interleukin-1b (IL-1b) (IC50=0.01 mM) [ 17] ib. Txawm li cas los xij, cov txheej txheem molecular hauv qab cov teebmeem ntawm triptolide ntawm cov noob pro-inflammatory tsis tau nkag siab tag nrho. XPB/ERCC3, subunit ntawm qhov transcription factor TFIIH, raug txheeb xyuas raws li lub hom phiaj ntawm COX-2. Triptolide hinders RNA Polymerase II-mediated transcription thiab nucleotide excision kho los ntawm lub hom phiaj XPB / ERCC3, yog li qhia los tiv thaiv proliferative thiabtiv thaiv-mobkev ua si [18]. Ntxiv mus, triptolide txhawb nqa pancreatic cancer cell apoptosis ntawm inhibition ntawm tshav kub poob siab protein 70 (HSP 70) [19]. Ntxiv mus, ntev triptolide (0.2 mg / kg / d rau 60 hnub) kev tswj hwm hauv nas tau tshaj tawm tias inhibit pancreatic cancer loj hlob thiab metastasis [19].

Rau cov neeg nyob hauv lub raum, triptolide tiv thaiv podocytes los ntawm puromycin aminonucleoside (PAN) [20] thiab C5b-9 [21] raug mob los ntawm inactivating reactive oxygen hom (ROS) kho p38 mitogen-activated protein kinase (MAPK) txoj kev. Inactivated human proximal tubular epithelial cells, triptolide suppresses C3, CD40, thiab B7h kab lus los ntawm kev tiv thaiv kab mob thiab kev tiv thaiv kab mob. Triptolide zoo dua li cyclosporine A thiab tacrolimus hauv inhibition ntawm C3 qhia [22].

Triptolide muaj txiaj ntsig zoo hauv ntau cov qauv proteinuria, xws li PAN-induced focal segmental glomerular sclerosis [20], passive Heymann nephritis [21], thiab mob ntshav qab zib nephropathy [23]. Hauv autosomal dominant polycystic raum kab mob (ADPKD), triptolide zoo txo cystogenesis thiab tiv thaiv lub raum ua haujlwm [24].

Kev nce qib tsis ntev los no: Hauv kev hloov pauv hauv nas lub raum allograft, triptolide inhibits tus neeg pub khoom tshwj xeeb cov tshuaj tiv thaiv kab mob thiab kev tiv thaiv kab mob hauv lub cev, txo qis cov tshuaj tiv thaiv rau lub raum kev raug mob los ntawm ob qho tib si hauv lub cev thiab hloov lub cev tiv thaiv kab mob [25].

2.1.2. Celastrol

CLT, ib qho triterpene, tau pom thawj zaug tias yog ib qho tshuaj tiv thaiv kub hnyiab protein 90 (HSP 90) inhibitor hauv prostate cancer hlwb, los ntawm inducing degradation ntawm HSP 90 [26]. CLT tseem txhawb nqa lub dephosphorylation thiab degradation ntawm HSP90 / CDC37 cov neeg siv cov protein kinases, uas inhibits cellular proliferation tab sis nce cellular apoptosis [27].

CLT muaj txiaj ntsig zoo hauv ischemia-reperfusion-induced mob raum raug mob (AKI) nas los ntawm inhibition ntawm kev txhais lus nuclear ntawm nuclear factor-kappaB (NF-kB) p65 [28]. CLT tseem hu ua cov khoom muaj zog tiv thaiv fibrotic. Nws alleviates lub raum fibrosis nyob rau hauv unilateral ureteral obstruction (UUO) nas qauv los ntawm upregulating cannabinoid receptor 2 qhia, uas yog ib tug tshwj xeeb metabotropic receptor ntawm lub endocannabinoid system ua si ib tug tseem ceeb luag hauj lwm nyob rau hauv o thiab fibrosis txheej txheem [29].

CLT muaj txiaj ntsig zoo hauv kev kho CKD, tab sis nws cov tshuaj toxicity, uas yog los ntawm TwHF tsis tuaj yeem tsis quav ntsej. Tsis ntev los no, CLT-loaded albumin nanoparticles tau pom kom txo tau cov tshuaj lom ntawm CLT hauv Thy1.1 mesangial proliferative glomerulonephritis nas qauv los ntawm lub hom phiaj mesangial hlwb [30].

Cistanche for kidney diease

cistanche siv rau dab tsi: txhawm rau txhim kho lub raum ua haujlwm

2.2. Astragaloside IV

Astragalus, tseem hu ua Huangqi, yog muab los ntawm cov hauv paus hniav ntawm Leguminosae cog Astragalus membrane los yog Astragalus mongo. Nyob rau hauv xyoo tas los no, Astragalus tau tshaj tawm tias muaj kev koom tes hauv kev tiv thaiv kab mob, immunostimulant, antioxidative, anticancer, thiab tshuaj tiv thaiv kab mob [31]. Nws kuj tau siv rau kev kho mob raum rau ntau dua 2,000 xyoo, uas tau sau tseg hauv Shen Nong's Materia Medica [31].

Astragaloside IV (AS-IV) yog ib qho ntawm ntau tshaj plaws thiab nquag sib xyaw ua ke ntawm Astragalus, nrog rau kev tiv thaiv kab mob muaj zog [32]. Luv luv, nws inactivates glycation kawg khoom-stimulated macrophages ntawm phosphate-p38 MAPK thiab NF-kB txoj kev [33]. AS-IV tuaj yeem ua rau T, B lymphocyte proliferation hauv vitro [34]. AS-IV alleviates T regulatory hlwb suppression los ntawm proinflammatory cytokine siab mobility pawg box 1 protein nyob rau hauv vitro [35].

Rau lub raum parenchyma hlwb, AS-IV attenuates glycated albumin-induced epithelial-mesenchymal hloov (EMT) nyob rau hauv NRK-52E cell kab ntawm balancing redox [34]. AS-IV tuaj yeem cuam tshuam cov piam thaj siab (HG) ua rau cov cell apoptosis los ntawm kev txo qis p38 MAPK txoj hauv kev hauv tib neeg cov hlab ntsha epithelial [36]. AS-IV txhim kho HG-induced podocyte dysfunction ntawm a3b integrin upregulation thiab integrin-linked kinase inhibition [37].

Rau cov qauv tsiaj, AS-IV tiv thaiv AKI hauv ischemia-reperfusion thiab sib piv-induced AKI nas thiab cisplatin (CP)-mediated AKI nas los ntawm inhibiting oxidative stress thiab apoptosis [38,39]. AS-IV kuj ua kom lub raum raug mob hauv cov kab mob streptozotocin-induced ntshav qab zib nas los ntawm inhibition of o induced by the NF-kB pathway [40].

Kev nce qib tsis ntev los no: AS-IV tau pom tias inhibit miR-21-induced podocyte dedifferentiation thiab mesangial cell activation, yog li txhim kho lub raum ua haujlwm thiab txo qis fibrosis hauv cov nas mob ntshav qab zib [41].

2.3. Emodin thiab Rhein

Rheum Officinale (Da Huang), cov nroj tsuag tshuaj ntsuab, tau siv dav hauv Suav teb rau nws cov nyhuv cathartic muaj zog. Tsis ntev los no, nws tau siv los ua kom qeeb ntawm CKD. Cov txheej txheem koom nrog hauv kev kho CKD suav nrog squalene epoxidase inhibition [42] thiab cov nyhuv anti-fibrotic [43]. Emodin thiab Rhein yog ob qho tseem ceeb tshaj plaws uas cais tawm ntawm Rheum Officinale [44].

2.3.1. Emodin

Emodin nthuav tawm ntau yam khoom siv tshuaj, xws li tshuaj tiv thaiv apoptosis, tiv thaiv oxidant, tiv thaiv EMT, tiv thaiv fibrosis, thiab tiv thaiv kev ua xua. Hauv kev nthuav dav, emodin ameliorates CP-induced apoptosis ntawm nas lub raum tubular hlwb hauv vitro los ntawm kev hloov kho AMPK / mTOR signaling pathway [45]. Ntxiv mus, nws tiv thaiv oxidative kev nyuaj siab thiab hypoxia / reoxygenation-induced apoptosis ntawm HK-2 hlwb [46]. Emodin ameliorates HG-induced podocyte EMT [47]. Emodin attenuates HG-induced transforming growth factor-beta 1 (TGF-b1) thiab fibronectin qhia hauv mesangial hlwb los ntawm inhibition ntawm txoj kev NF-kB [48]. Emodin suppresses HG-induced proliferation thiab fibronectin qhia nyob rau hauv nas mesangial hlwb ntawm p38 MAPK txoj kev [49].

Emodin muaj txiaj ntsig zoo hauv LPS induced AKI los ntawm kev cuam tshuam ntawm kev mob thiab kev hu xov tooj zoo li 2 txoj hauv kev [50]. Nws tiv thaiv kev mob ntshav qab zib nephropathy hauv cov qauv nas kho los ntawm PI3K/Akt/ GSK-3b thiab Bax/caspase-3 txoj kev taw qhia [51]. Ntxiv mus, nws muaj txiaj ntsig zoo hauv CP-induced nephrotoxicity hauv nas [52].

2.3.2. Rhein

Rhein nthuav tawm ntau yam kev tiv thaiv lub raum; Txawm li cas los xij, cov txheej txheem hauv qab no tsis tau txiav txim siab tag nrho. Hauv vitro, nws inhibits autophagy hauv nas lub raum tubular hlwb los ntawm kev tswj cov AMPK / mTOR signaling pathway [53]. Rhein txhawb nqa tus xov tooj zoo li receptor 4 proteolysis thiab txo qis lipopolysaccharide-induced AKI los ntawm kev khaws cia ntawm Klotho [54]. Rhein restores Klotho abundance nyob rau hauv adenine-induced CKD nas, uas feem ntau yog kho los ntawm demethylation txhawb nqa [55]. Rhein thim rov qab Klotho kev tawm tsam, uas cuam tshuam nrog DNA hypermethylation, yog li ameliorating lub raum fibrosis hauv nas [56]. Kev tiv thaiv cov teebmeem ntawm rhein tau pom ntawm UUO nephropathy nas [57].

cistanche health benefit

cistanche cov txiaj ntsig kev noj qab haus huv: kho cov kab mob raum

2.4. H1-A

Cordyceps Sinensis (CS), tseem hu ua Suav kab ntsig fungus, muaj txiaj ntsig zoo hauv kev hloov kho lub cev tiv thaiv kab mob [58]. CS tau siv dav los ua cov tshuaj ntsiav tshuaj rau cov neeg mob CKD.

H1-A, yog ib qho ntawm cov metabolites loj thib ob los ntawm CS [58], ua lub luag haujlwm tseem ceeb hauv kev cuam tshuam ntawm tib neeg mesangial cell proliferation. Nws txhawb nqa cellular apoptosis los ntawm suppressing tyrosine phosphorylation ntawm Bcl-2 thiab Bcl-XL [59,60]. H1-A kuj tseem siv tau rau IgA nephropathy nrog kev kho mob thiab kev txhim kho histological [60].

2.5. Saikosaponin d

Radix bupleuri (Chai hu) yog cov cag qhuav ntawm Bupleurum chinense DC. thiab Bupleurum scorzonerifolium Willd [61]. Triterpenoid saponins yog cov tseem ceeb bioactive Cheebtsam muab rho tawm los ntawm Radix bleu [62], uas Daikin d (SSD) yog ib qho tseem ceeb tshaj plaws Saiko saponins, nrog rau kev tiv thaiv, antitumor, thiab immunoregulation kev ua ub no [63].

SSD, hu ua sarcoplasmic / endoplasmic reticulum Ca2 ntxiv rau ATPase twj tso kua mis inhibitor, induces autophagic cell tuag nyob rau hauv apoptosis-tshuaj hlwb [64]. Nws inhibits proliferation los ntawm up-regulating autophagy ntawm CaMKKb-AMPK-mTOR txoj hauv kev hauv ADPKD hlwb [65].

SSD txo CP-induced nephrotoxicity los ntawm repressing ROS-mediated activation ntawm MAPK thiab NF-kB signaling pathways [66]. Nws kuj ua rau mesangial hlwb proliferation inhibition, tab sis tsis cell tuag, uas yog kho los ntawm downregulation ntawm CDK4, c-Jun, thiab c-Fos [67]. SSD muaj txiaj ntsig zoo hauv Thy1.1-induced metro cov ntaub ntawv glomerulonephritis los ntawm kev txo TGF-b1 abundance thiab inflammatory cells [68].

2.6. Poricoic acid ZA

Cov sclerotia qhuav ntawm Poria cocos Hma (WPC) tau siv los kho mob edema thiab nephrosis. WPC txhim kho PAN-induced nephrosis los ntawm inhibition ntawm dej thiab sodium raws, yog li txhim kho edema thiab nephrosis [69]. WPC inhibits HG-induced proliferation ntawm nas mesangial hlwb [70]. Portico acid ZA, ib qho tshiab RAS inhibitor, yog muab rho tawm los ntawm WPC. Nws attenuates interstitial fibrosis thiab podocyte raug mob los ntawm inhibiting TGF-b / Smad signaling pathway [71].

3. Kev xav

TCM, ntawm ib sab, muaj cov teebmeem kev kho mob hauv CKD, ntawm qhov tod tes, cov tshuaj toxicity ntawm cov tshuaj ntsuab tsis tuaj yeem tsis quav ntsej [5]. Kev ntsuas detoxifying cov tshuaj ntsuab nyob rau hauv txoj kev qub, uas yog hu ua 'PaoZhi' hauv Suav, tuaj yeem txo cov tshuaj toxicity los ua TCMs [72]. Ntxiv mus, kev sib raug zoo ntawm TCMs yog lub hauv paus ntsiab lus ntawm Monarch-Minister Assistant-Guide, uas tseem hu ua 'Jun-Chen-Zuo-Shi' hauv Suav. Cov pab yog cov tshuaj ntsuab, uas muaj cov nyhuv antagonist ntawm toxicity ntawm TCM tshuaj [73].

Rau qhov pom ntawm cov kws tshuaj niaj hnub no, kev sib cais ntawm cov tshuaj muaj txiaj ntsig zoo thiab cov tshuaj lom neeg tuaj yeem ua rau muaj kev tsim nyog rau TCMs. Txawm li cas los xij, qee cov tshuaj muaj txiaj ntsig zoo, xws li triptolide thiab cestrol, kuj muaj cov tshuaj lom neeg ua haujlwm. Kev tshawb nrhiav ntxiv rau qhov ntau npaum li cas thiab lub sijhawm xav tau kev sim tshuaj. Thiab vector, uas tuaj yeem txo cov tshuaj lom ntawm cov tshuaj, yog ib qho ntawm cov lus qhia yav tom ntej [30].

4. Cov lus xaus

TCMs muaj keeb kwm ntev hauv kev kho mob CKD. Txawm hais tiasTCMs tau siv dav hauv tsev kho mob hauv Suav teb, lawv cov txheej txheem tseeb ntawm lawv tsis nkag siab tag nrho. Tsis tas li ntawd, daim ntawv thov ntawm TCM feem ntau yog ua raws li kev paub ntawm tus kheej, uas tsis muaj cov qauv ntsuas ntsuas. Kev rho tawm thev naus laus zis muab kev nkag siab tshiab rau hauv daim ntawv thov ntawm TCMs. Ntau cov tebchaw muaj txiaj ntsig zoo tau ua pov thawj tias muaj kev tiv thaiv kab mob, tiv thaiv oxidative, lossis immunomodulatory teebmeem. Qee qhov ntawm lawv tsis tsuas yog muaj kev tiv thaiv ntawm lub raum parenchymal hlwb ncaj qha tab sis kuj tseem siv tau zoo hauv cov qauv tsiaj. Cov khoom zoo nkauj no muaj peev xwm txhais tau zoo rau kev siv TCMs. Tsis tas li ntawd, kev sim tshuaj loj yog xav tau rau TCMs thiab lawv cov extractions hauv CKD kho.

Kev nthuav tawm ntawm kev txaus siab

Cov kws sau ntawv tshaj tawm tias lawv tsis muaj kev sib tw nyiam.

Kev lees paub

Txoj haujlwm no tau txais kev txhawb nqa los ntawm National NaturalScience Foundation ntawm Tuam Tshoj (No. 81974096, No. 81961138007, No.81770711), National Key R&D Program of China (2018YFC1314000), thiab Program rau HUST Academic Frontier01QY Team (2TD.

Cistanche for treating kidney disease