Combined extract (Curcuma longa-Glycyrrhiza glabra) alleviates the inflammations of Achilles tendinopathy in Wistar rats.

OBJECTIVE: Achilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats). MATERIALS AND METHODS: This study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation. RESULTS: After Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels. CONCLUSIONS: We found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

Metabolite extract of Streptomyces hygroscopicus Hygroscopicus inhibit the growth of Plasmodium berghei through inhibition of ubiquitin - proteasome system.

Streptomyces hygroscopicus Hygroscopicus, a member of family of Actinomycetes produces eponemycin a proteasome inhibitor that can inhibit Ubiquitin-Proteasome System (UPS) function in eukaryotic cell. Previous study showed that coronamycin, an active substrate isolated from Streptomyces sp. can act as anti-plasmodial, antibacterial, and antifungal, however the research did not show the mechanism of coronamycin in inhibiting the growth of Plasmodium. This research was done to reveal if eponemycin that is contained in metabolite extract of S. hygroscopicus can inhibit UPS function of Plasmodium berghei. This study was an experimental study using P. berghei infected Balb/C mice as malaria model. Samples were divided into 1 control group (group infected with P. berghei without treatment) and 3 treatment groups (mice infected with P. berghei and treated intra-peritoneal with metabolite extract of S. hygroscopicus dose 130 µg/kgBW, 580 µg/kgBW, and 2600 µg/kgBW for 5 days). The degree of parasitemia and morphology of the parasite were measured from the first day of malaria induction until the last treatment. The accumulation level of polyubiquitin was measured using Western blot and ELISA method. The degree of parasitemia on day 6 showed significant differences among treatment groups and control (p=0,000). Percentage of inhibition showed significant differences between control and group treated with metabolite extract of S. hygroscopicus 2600 µg/kgBW. An increasing dose of extract of S. hygroscopicus followed by an increasing of inhibition in parasite growth (r=0,850). Probit analysis showed that ED50 was 9.418 µg/kgBW. There was a change in morphology of the parasite after treatment. Parasite morphology became crisis form. There was an accumulation of polyubiquitinated protein in the group treated with metabolite extract of S. hygroscopicus 2600 µg/kgBW. It can be concluded that analog eponemycin in metabolite of S. hygroscopicus is a potential candidate for new malarial drug by inhibiting UPS function of the parasite and cause stress and dead of the parasite.

High dose of N-acetylcysteine increase H2O2 and MDA levels and decrease GSH level of HUVECs exposed with malaria serum.

Dysfunction of endothelial cells in severe malaria may result from excessive activation of tumor necrosis factor (TNF)-α which leads to an increase in production of reactive oxygen species (ROS) and decrease of antioxidant level of endothelial cells. To investigate the effect of N-acetylcysteine (NAC) on hydrogen peroxide (H2O2), malondialdehyde (MDA) and glutathione (GSH) levels produced by endothelial cells exposed with serum of malaria falciparum patient, an in vitro model of human umbilical vein endothelial cells (HUVECs) culture was used. Sample groups were normal HUVECs (group A), HUVECs that was exposed with malaria serum without any treatment (group B), HUVECs that were exposed with malaria serum and treated with NAC 2 µM (group C), HUVECs that were exposed with malaria serum and treated with NAC 4 µM (group D), and HUVECs that were exposed with malaria serum and treated with NAC 8 µM (group E). The level of MDA was measured by thio-barbituric acid reaction assay and H2O2 level was measured by NWLSS Hydrogen Peroxyde/Peroxydase Assay kit. The level of GSH was determined by using NWLSS Glutathione Assay kit. The level of H2O2 and MDA decreased after administration of low dose of NAC. Unfortunately, increased H2O2 and MDA levels were found on HUVECs treated with high dose of NAC (8 µM). There was a positive correlation between NAC dose and H2O2 level (r= 0,603) and between NAC dose and MDA level (r= 0,721). A significant decreased level of GSH was found on HUVECs treated with high dose of NAC (p = 0,023). It can be concluded that the use of high dose of NAC as supportive therapy in severe malaria infection must be taken carefully.