Depressed calcium-handling proteins due to endoplasmic reticulum stress and apoptosis in the diabetic heart are attenuated by argirein.

Diabetic cardiomyopathy (DC) is a unique disease frequently complicated to diabetes mellitus, manifesting endoplasmic reticulum (ER) stress and depressed calcium-handling proteins. We hypothesized that the abnormal FKBP12.6, SERCA2a, and CASQ2 are consequent to ER stress and apoptosis that are likely due to an entity of inflammation. These abnormalities may be attributed to reactive oxygen species genesis from activated NADPH oxidase which could respond to argirein (AR) through its anti-inflammatory activity. Sprague Dawley rats were randomly divided into six groups. Except the normal group, rats were injected with streptozotocin (STZ; 60 mg/kg, i.p.) once. During weeks 5 to 8 following STZ injection, rats were treated (in milligrams per kilogram per day, i.g.) with aminoguanidine (AMG, 100; an inducible nitric oxide synthase and AGEs inhibitor) or three doses of AR (50, 100, and 200). FKBP12.6, SERCA2a, and CASQ2 and ER stress chaperones Bip and PERK and apoptotic molecules were monitored in vivo and in vitro. Impaired cardiac performance and downregulated FKBP12.6, SERCA2a, and CASQ2 were significant in DC in vivo, and abnormal calcium-handling proteins were also found in high-glucose-incubated myocytes in vitro. ER stress manifested by upregulated Bip and PERK was predominant in association with DNA ladder and upregulated Bax and downregulated BCL-2 in vivo and in vitro. AR is effective to attenuate these abnormalities compared to AMG. Diabetic myocardium has inflammatory entity expressed as ER stress contributing to downregulated calcium-handling proteins. AR has potential in managing DC through attenuating depressed calcium-handling proteins, activated ER stress, and apoptosis in the myocardium.

Argirein alleviates diabetic nephropathy through attenuating NADPH oxidase, Cx43, and PERK in renal tissue.

Diabetic nephropathy (DN) due to microvascular complication is a serious status characterized by continuously progressive until occurrence of the end stage of renal disease. It is attractive to investigate further mechanisms underlying the entity of DN and new drug discovery. We hypothesized that the entity of DN is inflammatory and is characterized by upregulated inflammatory/pro-inflammatory factors such as peroxisome proliferator-activated receptor alpha, NADPH oxidase, endoplasmic reticulum stress (ER stress), and endothelin receptor A (ET(A)) and downregulated connexin 43 (Cx43) in the kidney. Aminoguanidine is a special blocker to advanced glycation end products and argirein, a new compound contains a molecule of rhein linked to L: -arginine by a hydrogen bond. Rhein possesses anti-inflammatory activity and has been chemically modified to produce a new compound diacerein launched in European market for treating osteoarthritis. Argirein with two active molecules rhein and L: -arginine may be effective in suppressing the inflammatory cytokines contributing to the pathogenesis of DN. With a single injection of streptozotocin 65 mg/kg, ip in rats, early diabetic nephropathy was produced and revealed as an increased microalbuminuria, elevated creatinine and urea in serum, associated with upregulation of mRNA and protein of NADPH oxidase p22phox, p47phox, and p67phox and ET(A), upregulated PKR-like eukaryotic initiation factor 2α kinase (PERK), and downregulated Cx43 in the renal tissue. Upregulation of PERK suggested that there is an ER stress involved in the diabetic kidney, along with an increase in inflammatory/pro-inflammatory factors indicating an entity of chronic inflammation. Abnormalities of biomarkers were blunted by either aminoguanidine or argirein significantly. The new compound argirein is potential in alleviating and retarding microvascular complications of diabetes such as DN in clinical settings.

[Pharmacognostical studies on Baibu radix stemonae and allied drugs. IX. Determination and evaluation of total alkaloid content in the roots of Chinese Stemona spp].

An acid-dye colorimetric method was reported for the determination of total alkaloids in 53 samples of Baibu drugs from their growing destricts in 14 provinces and municipalities and its average recovery and its linear range were 96.1% (CV less than 4%) and 20-150 micrograms respectively. The relationship between the total alkaloid content, geographical origins and morphology were discussed. The results showed that: 1. the content of total alkaloids of stemona was 0.26-3.1%; 2. that of Stemona sessilifolia was 0.26-2.17% with the highest content of the sample from Nanyang country in Henan Province; 3. that of S. japonica was 0.83-1.43%; 4. that of S. tuberosa was 0.53-3.1% with the highest content of sample from Hengyang in Hunan Province; 5. that of S. parviflora was 0.22-0.74% with the highest content of sample from Qongzhong in Hainan Province; and 6. that of more yellow, solider and stronger samples was higher than that of any other samples. However, that of all bigger samples in shape was not higher than that of smaller ones.