Maria Apriliani Gani

Context: Scientific verification of the anti-hyperglycemic potential of Kayu sarampa (Xylocarpus moluccensis), which is popularly used for diabetic medication in North Sulawesi, Indonesia, is strongly important to conduct to avoid inappropriate medication that might cause worse conditions. Aims: To investigate the anti-hyperglycemic potential of X. moluccensis stem bark ethyl acetate extract and isolated compounds through the α-glucosidase enzyme inhibitory and antioxidant capacity determination. Methods: The active compound was isolated from ethyl acetate extract of X. moluccensis stem bark. The structures of those compounds were elucidated by infrared spectroscopy, liquid chromatography–mass spectrometry, and nuclear magnetic resonance spectroscopies. To discover the anti-hyperglycemic potency, α-glucosidase enzyme inhibition assay, antioxidant assay (DPPH and FRAP), and in silico study were performed. Results: Three isolated compounds were obtained and characterized as two tetrahydroxyterpenoids compounds, namely xyloccensin E (1) and ruageanin D (2), and one flavonoid compound, namely 3,5,7,3ʹ,4ʹ-pentahidroxyflavan (catechin) (3). Compounds 1 and 3 inhibited the α-glucosidase enzyme with IC50 values of 118.60 and 55.19 µg/mL, respectively, with a competitive inhibition mechanism. This is also in line with in silico findings, and both compounds showed good binding affinity of α-glucosidase protein, which indicated their anti-hyperglycemic activity potential by inhibiting α-glucosidase enzyme. Moreover, compounds 1 and 3 showed antioxidant capacity through the DPPH method with an IC50 value of 54.69 and 2.87 µg/mL. In addition, 100 µg/mL of compounds 1 and 3 also exhibited antioxidant capacity through the FRAP method with values of 66.35 and 213.82 µmol Fe2+/g, respectively. Conclusions: The X. moluccensis stem bark ethyl acetate extract, and isolated compounds exhibit α-glucosidase enzyme inhibitory activity and antioxidant capacity, which confirms its potency as an alternative medication for hyperglycemia issues.

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA–GEL (bovine hydroxyapatite–gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA–GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA–GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA–GEL pellet implants.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and emergency. Currently, there is no therapeutic agent that has been proven effective against the virus. Objective: We investigated and screened for 401 antiviral compounds that could inhibit one or more of the three protein targets in SARS-CoV-2 chymotrypsin-like (3CL) protease, RNA-dependent RNA polymerase, and spike glycoprotein) using the in-silico approach. Methods: Lipinski’s rule of five was used as an initial screening for relevant compounds. Ligand preparation was conducted using JChem software and Schrödinger’s LigPrep module, while protein elucidation was conducted using AutoDockTools-1.5.6. Molecular docking was analyzed using AutoDockVina. Results: Five antiviral compounds were obtained from each SARS-CoV-2 protein with ideal and potential binding energy as a candidate for target protein inhibition on SARS-CoV-2, TAK-981; lopinavir, mefloquine, and sitagliptin were potent inhibitors of 3CL protease; imatinib, relacatib, AZD7986, imatinib, and TAK-981 proteins showed potential as inhibitors of RdRp tetrandrine, and, selinexor, imatinib, lopinavir, and ciclesonide, showed potential as inhibitors of glycoprotein AZD7986. These compounds have better binding energy than the three comparator drugs, remdesivir, chloroquine, and hydroxychloroquine. Conclusion: We obtained several antiviral compounds with reliable binding energies to the SARSCoV- 2 proteins and potentially better efficacy than the three comparator drugs. Furthermore, this research will help accelerate the development of Covid-19 drugs.

Submicron hydroxyapatite has been reported to have beneficial effects in bone tissue engineering. This study aimed to fabricate submicron-scale bovine hydroxyapatite (BHA) using the high-energy dry ball milling method. Bovine cortical bone was pretreated and calcined to produce BHA powder scaled in microns. BHA was used to fabricate submicron BHA with milling treatment for 3, 6, and 9 h and was characterized by using dynamic light scattering, scanning electron microscope connected with energy dispersive X-Ray spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffractometry to obtain its particle size, calcium-to-phosphorus (Ca/P) ratio, functional chemical group, and XRD peaks and crystallinity. Results showed that the particle size of BHA had a wide distribution range, with peaks from ~5 to ~10 µm. Milling treatment for 3, 6, and 9 h successfully gradually reduced the particle size of BHA to a submicron scale. The milled BHA’s hydrodynamic size was significantly smaller compared to unmilled BHA. Milling treatment reduced the crystallinity of BHA. However, the treatment did not affect other characteristics; unmilled and milled BHA was shaped hexagonally, had carbonate and phosphate substitution groups, and the Ca/P ratio ranged from 1.48 to 1.68. In conclusion, the fabrication of submicron-scale BHA was successfully conducted using a high-energy dry ball milling method. The milling treatment did not affect the natural characteristics of BHA. Thus, the submicron-scale BHA may be potentially useful as a biomaterial for bone grafts.

Bone defects and periodontal disease are pathological conditions that may become neglected diseases if not treated properly. Hydroxyapatite (HA), along with tricalcium phosphate and bioglass ceramic, is a biomaterial widely applied to orthopedic and dental uses. The in vivo performance of HA is determined by the interaction between HA particles with bone cells, particularly the bone mineralizing cells osteoblasts. It has been reported that HA-induced osteoblastic differentiation by increasing the expression of osteogenic transcription factors. However, the pathway involved and the events that occur in the cell membrane have not been well understood and remain controversial. Advances in gene editing and the discovery of pharmacologic inhibitors assist researchers to better understand osteoblastic differentiation. This review summarizes the involvement of extracellular signal-regulated kinase (ERK), p38, Wnt, and bone morphogenetic protein 2 (BMP2) in osteoblastic cellular regulation induced by HA. These advances enhance the current understanding of the molecular mechanism of HA as a biomaterial. Moreover, they provide a better strategy for the design of HA to be utilized in bone engineering.

Osteomyelitis is an infectious disease which is also a major complication of bone defects. This study aims to determine the effect of bovine hydroxyapatite-gelatin-based bone implants with gentamicin as an antibiotic (BHA-GEL-GEN implant) on the regeneration of bone defects in vivo. The BHA-GEL-GEN and BHA-GEL implants were made by direct compression. In vivo study was carried out with Wistar rats. The rats were divided into three groups: negative control, BHA-GEL implant, and BHA-GEL-GEN implants. The defect model used was the burr hole defect model with diameter 2.2mm and 2mm deep. After 2, 7, 14, and 28 days, the rats were sacrificed. Bone integrity was carried out using X-ray radiography. Radiological examination was performed using haematoxylin and eosin (HE) staining and immunohistochemical techniques with anti-vascular endothelial growth factor (VEGF) and anti-alkaline phosphatase (ALP) antibodies. Based on the radiograph, the implanted group had accelerated bone growth in the defect area. Semiquantitative data from HE staining showed that the implanted group had accelerated migration of osteoclasts, osteoblasts, and osteocytes in the defect area. The immunoreactive score showed that the BHA-GEL-GEN group had higher VEGF expression compared to two other groups. The three groups did not provide a significant difference in ALP expression. In conclusion, the BHA-GEL-GEN implant causes accelerated bone defects repair by accelerating tissue vascularity and does not interfere with the bone remodeling process. Therefore, the BHA-GEL-GEN implant is potentially a biomedical material for osteomyelitis therapy.

Bovine bone is a considerable source for the production of hydroxyapatite. The recent study reported a novel method to extract hydroxyapatite from bovine bone without producing hazardous residue. The bovine bones were cut and boiled in the opened chamber followed by boiling in pressurized tank. The bones were then soaked into 95% ethanol. Calcination was then conducted in 800°C, 900°C and 1,000°C, for 2 hours. The result was then grinded and sieved. The powder then was characterized using Fourier transform infrared (FT-IR), Scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD) to measure the purity of hydroxyapatite. It is concluded that the hydroxyapatite derived from this process showed 100% purity, resulting 35.34 ± 0.39% w/w from the wet bone weight and 72.3% w/w from the dried weight. The present extraction method has been proven to yield high amount of pure hydroxyapatite as well as reducing the use of hazardous reagent.