Synthesis of Icariin-Zinc and its Protective Effect on Exercise Fatigue and Reproductive System Related Glands in Male Rats.

Background: Icariin, a traditional Chinese medicine, plays a protective role in the treatment of exercise fatigue. Zinc, a trace element, plays an important role in the reproductive system. Therefore, we aimed to synthesize an Icariin-Zinc complex (by chemical means) and verify its protective effect on exercise fatigue and the reproductive system using animal experiments. Methods: The icariin-zinc complex was prepared by the reaction of icariin carbonyl and zinc ions (molar ratio 1:3). The molecular formula and structural formula of the complex were identified and tested. Fifty-six rats selected by swimming training were randomly divided into six groups: static control, exercise control, icariin, gluconate zinc (G-Zn group), icariin glucose zinc and icariin-zinc exercise ( low, high dose/L-E group, H-E group) groups. These groups respectively received the following doses: 1 ml/100 g, daily gavage with NS (for the first two groups), 45 mg/kg icariin, 110 mg/kg Gluconate Zinc, Icariin glucose zinc (45 mg/kg Icariin and 110 mg/kg Gluconate Zinc), 60 mg/kg icariin zinc and 180 mg/kg icariin zinc. After 3 weeks of gavage, we conducted 6 weeks of exhaustive swimming training. Test indices such as exhaustive swimming time of rats and body weight were evaluated after the last training exercise. The seminal vesicles, testes, and prostate gland were weighed, and their indices were calculated. The levels of testosterone (in the plasma) and glycogen (in the liver and muscle homogenates) were also evaluated using ELISA. Results: Compared with the static control group, the exhaustive swimming time of the rats in each group was prolonged. Compared with the other groups, the exhaustive swimming time of the L-E and H-E groups was significantly longer (p < 0.01); the Icariin-Zinc complex significantly increased the exhaustive swimming time of the rats. Compared with the static control group, the plasma testosterone content of the L-E and H-E groups increased significantly (p < 0.05). Compared with the exercise control group and G-Zn group, the plasma testosterone content of the H-E group also increased significantly (p < 0.01). The Icariin-Zinc complex significantly increased the serum levels of testosterone in rats. Compared with the control group, the muscle glycogen reserves of each group decreased, indicating that the muscle glycogen reserves of the rats decreased after swimming. Compared with other groups, the Icariin-Zinc complex can reduce the level of glycogen in the muscles, indicating that it can increase the utilization efficiency of glycogen in muscles. Compared with the static control and exercise control groups, the testicular weight of rats in the administration groups increased slightly. The Icariin-Zinc complex increased the testicular weight, indicating that the function of the reproductive system was improved to some extent. Conclusion: Icariin-Zinc can significantly prolong the exhaustive swimming time, improve exercise ability, and increase the plasma testosterone level (which is beneficial for improving the reproductive ability of male rats). Moreover, the beneficial effect of Icariin-Zinc on the glycogen content, testis index, and other reproductive system glands is dose-dependent.

Identification of vitamin B6 as a PD-L1 suppressor and an adjuvant for cancer immunotherapy.

Interaction of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibits T cell activation. Tumor tissues can evade immune surveillance by expressing higher levels of PD-L1. Identification of potential regulators of PD-L1 through natural metabolites may contribute to discovering new drugs for immunotherapy. By using a metabolite library screen, we showed that pyridoxal (PL) significantly suppresses PD-L1 expression. Mechanistically, PL accelerates PD-L1 degradation in a proteasome-dependent manner, and STUB1 serves as an E3 ligase during the process. Functionally, PL enhances T cell killing activity by blocking the PD-1/PD-L1 signaling pathway. Thus, we have identified PL as an inhibitor of PD-L1, which provides a feasible option for combination immunotherapy.

Icariin-conditioned serum engineered with hyaluronic acid promote repair of articular cartilage defects in rabbit knees.

BACKGROUND: Osteochondral defects mostly occur as a result of trauma or articular degeneration. The poor regenerative ability of articular cartilage remains osteochondral defects are a tricky problem to deal with. The modern treatment strategies mainly focus on cartilage tissue engineering with bioactive materials. In this study, we aimed to develop icariin conditioned serum (ICS) together with hyaluronic acid (HA) and determine their ability in reparing osteochondral tissue in a critical-sized defect in rabbit knees. METHODS: Primary chondrocytes were incubated with serum conditioned with icariin at different concentrations, then cell proliferation rates and glycosaminoglycan (GAG) secretion were detected. Rabbits were treated with intra-articular injection of 0.5 mL normal saline (NS), ICS, HA and ICS + HA in the right knee joint, respectively. ICRS scores were used to assess the macroscopic cartilage regeneration. Histological and immunohistochemical analysis including H&E, Safranin O, toluidine blue and collagen II staining were used to determine the repair of cartilage and the regeneration of chondrocytes. RESULTS: Icariin at a low dose of 0.94 g/kg was identified to have significantly promoted the proliferation of chondrocytes and enhance the secretion of GAG. Femoral condyle from rabbits treated by ICS together with HA was observed to be integrated with native cartilage and more subchondral bone regeneration. ICS together with HA could promote repair of the cartilage defect and increase the neoformation of cartilage. CONCLUSIONS: These results demonstrated the potential of ICS combined with HA to promote reparative response in cartilage defects and the possible application in bioactive material based cartilage regeneration therapies.