Effect of Kalanchoe crenata Extract on Renal and Liver Impairment, Dyslipedemia and Glycemia in Streptozotocin Induced Diabetic Rats

Introduction: Diabetes mellitus or diabetes is a metabolic ailment which occurs as a result of insulin insufficiency or defect in insulin function, or both that leads to ihyperglycemia. Diabetes mellitus is a worldwide disease even though its prevalence in other countries vary. Kalanchoe crenata belongs to the family crassulaceae. It is also known locally as miracle plant and often utilized in Africa for medicinal purposes. The study was designed to ascertain the antidiabetic and dyslipidemic activity and effects of the ethanolic extract of both leaves and stem of Kalanchoe crenata on istreptozotocin incite diabetic rats for three (3) weeks. Methodology: 6-8 weeks old Sprague dawley rats received multiple injection of streptozotocin intraperitoneally (40mg/kg body weight) to induce diabetes melitus. Diabetes mellitus was observed and confirmed after six days of induction. The rats were given ethanolic extract of Kalanchoe crenata remarkably (10, 30 and 100mg/kg) and 5mg/kg glibenclamide orally twice daily for three weeks. Blood glucose, lipids, creatinine, urea, were then determined. Results: After week three of treatment 5mg/kg glibenclamide, 30 and 100mg/kg ethanolic extract of Kalanchoe crenata remarkably (p<0.05) decrease glycemia and improved lipidemia by decreasing overall cholesterol, LDL-C and increasing HDL-C likened to the control diabetic group. Also results from treated rats remarkably decrease blood urea nitrogen and creatinine. However, the affirmative control and the sampled treated groups showed curative and regenerative effect in the cells responsible for producing endocrine insulin “beta cells of the islets of Langerhans” located in the pancreas. Kidney and liver tissue sections of treatment groups showed a reversal of diseased insults made by the streptozotocin. Conclusion: The outcome of the research indicate that given ethanolic extract of Kalanchoe crenata remarkably contains the necessary phytochemicals for the development of a standard and effective herbal medicine for Diabetes mellitus and related complications and also with no toxic effects on the tissues of the liver, pancreas and kidney.

Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells (rBMMSCs) in Collagen Type I Containing Platelet-Rich Plasma for Osteoarthritis Treatment in Rat Model

Osteoarthritis (OA) is the most common form of degenerative joint disease, affecting more than 25% of the adult though prevalent in the elderly population. Most of the current therapeutic modalities aim at symptomatic treatment and lingering the disease progression. In recent years, regenerative medicine such as stem cell transplantation and tissue engineering has been suggested as a potential curative intervention for OA. The objective of current study was to assess the safety and efficacy of an injectable tissue-engineered construct composed of BMMSCs, PRP, and Collagen type I in rat model of OA.To produce collagen type I, PRP and BMMSCs, male Wistar rats were ethically euthanized. After expansion and characterization of rat BMMSCs (rBMMSCs), tissue-engineered construct was formed by combination of appropriate amount of collagen type I, PRP and rBMMSCs. In vitro studies were conducted to evaluate the effect of PRP on chondrogenic differentiation capacity of encapsulated cells. Then tissue-engineered construct was injected in knee joint of rat model of OA (24 rat in 4 groups:OA, OA+MSC, ‎OA+Collagen+MSC+PRP, OA+MSC+Collagen).After 6 weeks, the animals were euthanized and knee joint histopathology examinations were performed to evaluate the effect of each treatment on OA.Tissue-engineered construct was successfully manufactured and in vitro assays demonstrated that relevant chondrogenic genes and proteins expression were higher in PRP group than the others. Histopathological findings of the knee joint samples showed favorable regenerative effect of rBMMSCs+PRP+Collagengroup comparing to others.In this study, we introduced an injectable tissue-engineered product composed of rBMMSCs+PRP+Collagenwith potential regenerative effect on cartilage damage caused by OA.

Stem cell-free therapy for glaucoma to preserve vision

Glaucoma is the leading cause of irreversible blindness with trabecular meshwork (TM) dysfunction resulting in elevated intraocular pressure and retinal ganglion cell (RGC) damage leading to vision loss. In this study, we discovered that secretome, derived from human TM stem cells, via minimal invasive periocular injection, can reduce intraocular pressure, restore TM homeostasis, protect RGC, and restore RGC function in both steroid-induced and genetic myocilin mutant mouse models of glaucoma. The secretome upregulated the COX2-PGE2 axis via mitochondrial TMEM177 and led to activation of endogenous stem cells and TM regeneration. Inhibition of COX2 abolished the protective effect of secretome on TM cells. Secretome treatment also enhanced RGC survival and function. Proteomic analysis revealed that the secretome is enriched with proteins involved in extracellular matrix modulation leading to the remodeling of TM to restore homeostasis. This study highlights the feasibility of stem cell-free therapy for glaucoma with minimal invasive administration and the involvement of multiple novel pathways for a cumulative regenerative effect on the TM to protect RGC.

Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.