Comparing the pharmacological effects of the prepared folium of Epimedium brevicornu Maxim. and Epimedium sagittatum Maxim. on kidney-Yang deficiency syndrome and liver injury complications.

Yinyanghuo, a famous herb, includes the folium of Epimedium brevicornu Maxim. and Epimedium sagittatum Maxim. It is believed that their processed products, the prepared slices of the folium of Epimedium brevicornu Maxim. (PFEB) and Epimedium sagittatum Maxim. (PFES) have greater efficacy in tonifying kidney Yang to treat kidney-Yang deficiency syndrome (KDS). However, there are few studies comparing the pharmacological effects of PFEB and PFES, and the underlying mechanisms. This study compared their effects on improving hypothalamic-pituitary-adrenal (HPA) axis, immune system and sexual characteristic, as well as repairing liver injury complications in the KDS model mice. Additionally, the mechanisms of the effects relevance to their main components were explored. It was found that PFEB was more effective than PFES in increasing cAMP/cGMP ratio, SOD activity, CRH and ACTH levels, eNOS and testosterone levels, splenic lymphocytes proliferation, while in decreasing MDA content, atrophy of spleen and thymus, splenic lymphocytes apoptosis, and PDE5 level. PFES showed stronger protection than PFEB in decreasing triglyceride and hepatic lipid. The contents of baohuoside I and epimedin A, B were much higher in PFEB, while Epimedin C, Icariin, 2-O″-rhamnosylicaridide II were higher in PFES. Consequently, PFEB exhibits superior efficacy over PFES in tonifying the kidney-Yang by improving the neuroendocrine-immune network, including HPA axis, immune systems, and corpus cavernosum. However, PFES has better recovery effect on mild hepatic lipid caused by KDS. The efficacy difference between PFEB and PFES in kidney-Yang and liver may be attributed to the content variations of baohuoside I.

[Progress of studies on anti-breast tumor mechanism of alkaloids].

Breast tumor has become one of the malignant tumors with the highest incidence, and is a serious threat to human health, especially to women. Chemotherapy is an important anti-breast tumor therapy, which can be used in almost every stage of breast tumor therapy alone or in the combination with surgery and radiation therapy. Alkaloids are a kind of ubiquitous natural products, and important active components of various medicinal plants. A large number of studies have shown that alkaloids could exert an anti-breast tumor effect by inhibiting proliferation, metastasis and angiogenesis, resisting mitosis, promoting apoptosis and autophagy, and triggering cell cycle arrest. The extensive anti-breast tumor effect makes alkaloids an important candidate drug source. This paper reviews the anti-breast tumor mechanism of natural products of alkaloids.

Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus.

Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA), HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H). HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total cholesterol, triglyceride, fasting plasma insulin (FINS), and glucagon (FG) were determined, and an oral glucose tolerance test was performed. The expression patterns of proteins and genes associated with insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of HMS5552 on the liver and pancreas. Our data suggest that the novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.

Targeting and liposomal drug delivery to CD40L expressing T cells for treatment of autoimmune diseases.

CD40L is considered as an important target for the treatment of autoimmune diseases. There have been many efforts devoted to the development of antibodies and other molecules to disrupt CD40/CD40L interaction for therapeutic benefits. In this study, we designed a CD40L specific peptide ligand - A25 based on CD40L crystal structure and molecular docking studies. Its binding affinity and specificity to CD40L were confirmed by Surface Plasmon Resonance (SPR) measurements. The peptide A25 was then conjugated on the surface of liposomes and shown to be able to mediate specific liposomal drug delivery to CD40L+ cells. Loaded with the cytostatic drug methotrexate (MTX), the A25 modified liposome could significantly reduce the CD40L+ cell ratios in the experimental autoimmune encephalomyelitis (EAE) mice, resulting in great improvement in clinical scores. Since CD40L+ cells are involved in the pathological development of many auto-immune diseases, A25 conjugated drug targeting systems may be useful for developing therapies that are more efficacies and with less side effects.

Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection.

Actin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi actin shows 100%, 98.7%, and 93.1%, homology with Trypanosoma equiperdum, Trypanosoma brucei brucei, and Trypanosoma cruzi. Recombinant actin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant actin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818, and T. b. brucei STIB 940, showing 63.3%, 56.7%, and 53.3% protection, respectively. Serum collected from the rabbit immunized with recombinant actin inhibited the growth of T. evansi, T. equiperdum, and T. b. brucei in vitro cultivation. Serum from mice and rabbits immunized with recombinant actin only recognized T. evansi actin but not mouse actin. The results of this study suggest that the recombinant T. evansi actin induces protective immunity against T. evansi, T. equiperdum, and T. b. brucei infection and may be useful in the development of a vaccine with other cytoskeletal proteins to prevent animal trypanosomiasis caused by these three trypanosome species.