Diabetic Osteoporosis: A Review of Its Traditional Chinese Medicinal Use and Clinical and Preclinical Research

Aim. The incidence of diabetic osteoporosis (DOP) is increasing due to lack of effective management over the past few decades. This review aims to summarize traditional Chinese medicine (TCM) suitability in the pathogenesis and clinical and preclinical management of DOP. Methods. Literature sources used were from Medline (Pubmed), CNKI (China Knowledge Resource Integrated Database), and CSTJ (China Science and Technology Journal Database) online databases. For the consultation, keywords such as diabetic osteoporosis (DOP), TCM, clinical study, animal experiment, toxicity, and research progress were used in various combinations. Around 100 research papers and reviews were visited. Results. Liver-spleen-kidney insufficiency may result in development of DOP. 18 clinical trials are identified to use TCM compound prescriptions for management of patients with DOP. TCM herbs and their active ingredients are effective in preventing the development of DOP in streptozotocin (STZ) and alloxan as well as STZ combined with ovariectomy insulted rats. Among them, most frequently used TCM herbs in clinical trials are Radix Astragali, Radix et Rhizoma Salviae Miltiorrhizae, Radix Rehmanniae Preparata, and Herba Epimedii. Some of TCM herbs also exhibit toxicities in clinical and preclinical research. Conclusions. TCM herbs may act as the novel sources of anti-DOP drugs by improving bone and glucolipid metabolisms. However, the pathogenesis of DOP and the material base of TCM herbs still merit further study

Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis

Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.</jats:p