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Wednesday, 19 March 2014

Polycystic kidney disease in Herbs Points of View

Kyle J. Norton

Polycystic kidney disease, also known as polycystic kidney syndrome is a cystic genetic disorder (a)(b)(c) of the kidneys, classified into:
A. Autosomal dominant polycystic kidney disease (ADPKD) affects all ethnic groups with a prevalence of 1:400-1:1000 live births. The disease induced formation of  numerous cysts in the kidneys with progressively expand and eventually destroy normal kidney structure and function. And may be associated to other disease complications(1)
B. Autosomal recessive polycystic kidney disease (ARPKD) is genetic disorder due to mutation of gene in chromosomal locus 6p12.2., causing up to 50% of affected neonates die of pulmonary hypoplasia and specific changes in the kidney and liver. Children who survive neonatal period (from birth to 28 days of age)may be experience with decrease in kidney size (not affect the kidney function) and change in echogenicity occurs, producing a pattern similar to patients with autosomal dominant polycystic kidney disease(2).
Although the disease is due to gene mutation, according to the study by the West Virginia University, certain phytochemicals in foods and herbs have found effectively in  to attenuation of cyst pathogenesis in animal studies(3).

1. Thunder God Vine (Lei Gong Teng)
Lei Gong Teng is also known as Thunder god vine. The bitter and very toxic herb has been used in TCM as an anti-inflammatiory and immunosuppressive agent and to resolve toxins, treat proteinuric renal disease, etc., as it expels Wind-Damp, resolves edema, calms pain, etc., by enhancing the functions of Liver and kidney channels.
Triptolide, is a diterpenoid epoxide found in the Thunder God Vine or Tripterygium wilfordii. according to the study at Yale University, daily injections of a model of ADPKD with triptolide beginning on Day P16 significantly reduced the total number of cysts per kidney, with a pronounced effect on the number of microcysts and the overall cystic burden. At P22 and P35, the chemical compound also improve blood urea nitrogen levels(4),  renal function at postnatal day 8 by inhibition of the early phases of cyst growth(5).

2. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in trditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
Curcumin, a major chemical constituent found in turmeric, showed a profound effect in inhibition of  cyst progression, by improved renal histology and reduced STAT3 activation, proliferation index, cystic index, and kidney weight/body weight ratios, as well as significantly postponed renal failure in mice with severe PKD(6). Other study at the Peking University, showed to inhibit renal cyst formation through inhibited forskolin-promoted cell proliferation and promoted the tubule formation in MDCK (Madin-Darby canine kidney) cells(a possible tool for assessing the membrane permeability properties of early drug discovery compounds), which indicates curcumin promotes MDCK cell differentiation(7). Berberine, another chemical compound found in turmeric and palnts in berberis family exerted its AMP-activated kinase (AMPK) property in suppression of the over expression of rapamycin (mTOR) and cystic fibrosis transmembrane conductance regulator (CFTR) in patients with Polycystic kidney disease(8)(9).

3. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgolide B, a major chemical constituent of Ginkgo biloba, significantly inhibited MDCK cyst formation dose dependently and cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse mode, through induced cyst cell differentiation and altered the Ras/MAPK signaling pathway(10).

4. Stevia rebaudiana Bertoni (Sweetleaf) 
Stevia rebaudiana Bertoni, also known as sweetleaf is agenus of Stevia, belonging to the family  Asteraceae, native to subtropical and tropical regions from western North America to South America.The herb has been used in folk medicine in treating obesity, hypertension and heartburn, and to help lower uric acid levels(11). According to the joint study by the Mahidol University and Yale University School of Medicine, steviol found in Stevia rebaudiana Bertoni, suppressed CFTR and mTOR/S6K expression in renal cyst-lining epithelial cells, through stimulation of AMP-activated protein kinase (AMPK)(12).Other study also showed a positive effect of steviol in Madin-Darby canine kidney (MDCK) cyst enlargement by inhibiting CFTR channel activity and promoting proteasomal-mediated CFTR degradation(13).

5. San Leng
San Leng, a Chines herb, is also known as sparganum stoloniferum buch.-hams. The acrid, bitter and neutral herb has been used in TCM to promote blood clots, inhibit thrombosis, lower the  blood viscosity, etc. as it breaks up the Blood,  eliminates Blood accumulation, moves Qi. calms pain, etc. by enhancing the functions of liver and spleen channels. According to study by University of Alberta, the herb has also been used as a trial drug to treat polycystic kidney disease (PKD) patients in China. A recently study showed a positive effect against Polycystic kidney disease through reduced the proliferation of renal epithelial cells stimulated by epidermal growth factor (EGF), and inhibited the phosphorylation of the EGF receptor and possibly through inhibition of polycystin-L channel(14).

Taking altogether, the herbs above may be effective in reduced formation of renal cyst, inhibited  progression of the disease in patients with Polycystic kidney disease through some mechanisms, but large sample size and multi centers studies to identify the principle ingredients to validate these effectiveness are necessary. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.


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References
(a) Loss of Polycystin-1 Inhibits Bicc1 Expression during Mouse Development by Lian P1, Li A1, Li Y2, Liu H2, Liang D3, Hu B3, Lin D4, Jiang T5, Moeckel G6, Qin D7, Wu G8.(PubMed)
(b) Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations by Freedman BS1, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV.(PubMed)
(c) Polycystin-1 but not polycystin-2 deficiency causes upregulation of the mTOR pathway and can be synergistically targeted with rapamycin and metformin by Mekahli D1, Decuypere JP, Sammels E, Welkenhuyzen K, Schoeber J, Audrezet MP, Corvelyn A, Dechênes G, Ong AC, Wilmer MJ, van den Heuvel L, Bultynck G, Parys JB, Missiaen L, Levtchenko E, De Smedt H.(PubMed)
(1) Metabolic abnormalities in autosomal dominant polycystic kidney disease by Mao Z1, Xie G, Ong AC.(PubMed)
(2)  decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease by Blickman JG1, Bramson RT, Herrin JT.(PubMed)
(3) Evidence for a role of proteins, lipids, and phytochemicals in the prevention of polycystic kidney disease progression and severity by Maditz KH1, Gigliotti JC, Tou JC.(PubMed)
(4) Triptolide reduces cyst formation in a neonatal to adult transition Pkd1 model of ADPKD by Leuenroth SJ1, Bencivenga N, Chahboune H, Hyder F, Crews CM.(PubMed)
(5) Triptolide reduces cystogenesis in a model of ADPKD by Leuenroth SJ1, Bencivenga N, Igarashi P, Somlo S, Crews CM(PubMed)
(6) Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model by Leonhard WN1, van der Wal A, Novalic Z, Kunnen SJ, Gansevoort RT, Breuning MH, de Heer E, Peters DJ.(PubMed)
(7) Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways by Gao J1, Zhou H, Lei T, Zhou L, Li W, Li X, Yang B.(PubMed)
(7a) Activation of AMP-activated kinase as a strategy for managing autosomal dominant polycystic kidney disease by McCarty MF1, Barroso-Aranda J, Contreras F.(PubMed)
(7b) Berberine slows cell growth in autosomal dominant polycystic kidney disease cells by Bonon A1, Mangolini A, Pinton P, Del Senno L, Aguiari G.(PubMed)
(10) Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models by Zhou H1, Gao J, Zhou L, Li X, Li W, Li X, Xia Y, Yang B.(PubMed)
(11) Tanvir, Ashraf (24 May 2005). "Sugar Leav – A new breed of 'sweetener'". Pakistan Agricultural Research Council. Retrieved 2 January 2009.
(12) Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease by Yuajit C1, Muanprasat C2, Gallagher AR3, Fedeles SV3, Kittayaruksakul S4, Homvisasevongsa S5, Somlo S6, Chatsudthipong V7.(PubMed)
(13) Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation by Yuajit C1, Homvisasevongsa S, Chatsudthipong L, Soodvilai S, Muanprasat C, Chatsudthipong V.(PubMed)
(14) Inhibition of polycystin-L channel by the Chinese herb Sparganum stoloniferum Buch.-Ham by Li F1, Dai XQ, Li Q, Wu Y, Chen XZ.(PubMed)