Beneficial Effect of Corni Fructus, a Constituent of Hachimi-jio-gan, on Advanced Glycation End-product-Mediated Renal Injury in Streptozotocin-Treated Diabetic Rats

Abstract

Diabetes is a disorder of excessive urine excretion and chronic hyperglycemia, and glucose participates in diabetic complications such as atherosclerosis, cardiac dysfunction, and nephropathy. Chronic hyperglycemia accelerates activation of the formation of advanced glycation end-products (AGEs), oxidative stress, the polyol pathway, and protein kinase C pathway. These metabolic factors are synergistically correlated with one another; therefore, an effective treatment with wide-spread effects continues to be required.Up to now, there have been many experiments focusing on the treatment of diabetes and its complications with traditional medicines including Chinese prescriptions because of their absence of toxic and/or side-effects. In our previous study, we reported that the Chinese prescriptions Hachimijio-gan and Keishi-bukuryo-gan had potential therapeutic effects against diabetic nephropathy, and had different functions in terms of their effects on metabolic disorders, especially on AGE formation in Hachimi-jio-gan and oxidative stress in Keishi-bukuryo-gan. [1][2][3][4] In addition, we also clarified that administration of dried Rehmanniae Radix (Rehmannia glutinosa LIBOSCH. var. purpurea MAKINO) extract, which is the main constituent of Hachimi-jio-gan, attenuates renal dysfunction in diabetic nephropathy mainly due to its suppression of oxidative stress 5) ; however, for the analysis of this prescription, further characterization of the other constituents is needed. According to the three-dimensional HPLC profile, as previously shown, 2,4) morroniside, loganin, and paeoniflorin were detected as the major compounds in Hachimi-jio-gan. Morroniside and loganin are the components of Corni Fructus (Cornus officinalis SIEB. et ZUCC.) and paeoniflorin is the component of Moutan Cortex (Paeonia suffruticosa ANDREWS) common in Keishi-bukuryogan. Therefore, in order to clarify the source of a particular action of Hachimi-jio-gan, we chose to evaluate the usefulness of one of the crude drugs, Corni Fructus.Corni Fructus has been used as a traditional medicine in Japan and China, and the components of this plant are iridoid total glycoside such as morroniside and loganin and also a few polyphenols such as cornusiin A, B, and C, monomeric and trimeric hydrolysable tannins, and so on.6,7) Recently, it has been reported that Corni Fructus has a plasma glucoselowering action in normal rats, along with anti-neoplastic and anti-microbial effects.8-10) Moreover, Vareed et al. 11) also reported that Corni Fructus has been used for improving liver and kidney functions, and iridoid total glycoside has the effect of preventing the overexpression of transforming growth factor (TGF)-b 1 and matrixes in glomeruli with a diabetic model. 12) However, the mechanisms of Corni Fructus against glucose-associated metabolic disorders in diabetes have yet to be explored. To determine whether Corni Fructus possesses the principal role in Hachimi-jio-gan, which has a strong effect on AGE formation in diabetes and/or diabetic nephropathy, we e...

The Beneficial Effects of Morroniside on the Inflammatory Response and Lipid Metabolism in the Liver of <i>db</i>/<i>db</i> Mice

“…We have successively identified the main renoprotective active components of Corni Fructus through in vitro and in vivo studies. 14,17,26) Subsequently, the effect of morroniside on the type 2 diabetic liver, especially in the presence of dyslipidemia, which is not well known, was investigated in the present study.…”

“…Morroniside (20 or 100 mg/kg body weight per day) was orally administered using gavage to db/db mice (nϭ10, respectively), while vehicle db/db (nϭ10) and non-diabetic control m/m (nϭ6) mice received water for 8 weeks. The doses of morroniside were the same as our previous study using streptozotocin-induced diabetic rats, 17) which were determined according to our studies of Corni Fructus 14) and its fractions. 18) The body weight, food intake, and water intake were measured everyday during the treatment period.…”

“…is a rich source of iridoid glycosides in traditional medicine. 14) Iridoids are a group of natural products belonging to the terpenoids, which are ubiquitous in plants. However, only a limited number of taxa possess the enzymes that give rise to the cyclopentane ring that is characteristic of the carbocyclic iridoids.…”

“…We have successively identified the main renoprotective active components of Corni Fructus through in vitro and in vivo studies. 14,17,26) Subsequently, the effect of morroniside on the type 2 diabetic liver, especially in the presence of dyslipidemia, which is not well known, was investigated in the present study.The liver is an important organ for maintaining glucose and lipid homeostasis, and plays a critical role in regulating endogenous glucose production from de novo synthesis (gluconeogenesis) or the catabolism of glycogen (glycogenolysis). Increased rates of hepatic glucose production are largely responsible for the development of overt hyperglycemia.…”

The Renal Effects of Blood Glucose-Lowering Plant-Derived Extracts in Diabetes Mellitus—an Overview

“…[71] Cornus officinalis + ↓ Kidney ROS [72] Gongronema latifolium + ↑ Superoxide dismutase (SOD), glutathione peroxidase [73] Rheum emodi − (GPx), reduced glutathione (GSH), catalase, etc. [74] Vigna angularis − Renoprotection [75] Helicrysium ceres + Amelioration of renal function [76] Oleanolic acid (Syzygium cordatum) + ↑ GFR [77] Sclerocarya birrea + ↓ Plasma urea and creatinine concentrations [19] Opunthia megacantha + ↓ Urinary protein concentration [20] Persea americana + [78] Jawarishi Zarooni Sada (a polyherbal unani formulation) − [79] Corni fructus + Maintenance of kidney structure [80] Curcumin (Curcumin longa) + ↓ Kidney levels of RAGE, AGE, TGF-ß 1 [81] Allium sativum and Zingiber officinale + ↓ Extra-cellular matrix proteins (e.g., fibronectin) [82] Momordica charantia + ↓ Renal hypertrophy [26] Coptis chinensis and Phellodendron amurense + [49] Hypoxis hemerocallidea + Reno-toxic effects [66] Opunthia megacantha + ↓GFR↑ serum urea and creatinine concentrations [83] …”