Methods: Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.
Results: Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.
Conclusion: Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.
Materials and methods: Hepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied.
Results: Histopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents.
Conclusion: Cabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects.
METHODS: The produced formulations were evaluated based on particle size and shape (particle size distribution (PSD), scanning electron microscope (SEM)), incompatibility (differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)), drug release pattern, permeation behavior, in vivo hypoglycemic effects, and in vitro anticancer potential.
RESULTS: Compatibility studies concluded that there was minimal interaction between metformin HCl and the polymer, whereas SEM images revealed smoother, more spherical nanoparticles than microspheres. Drug release from the formulations was primarily controlled by the non-Fickian diffusion process, except for A1 and A4 by Fickian, and B3 by Super case II. Korsmeyer-Peppas was the best-fit model for the maximum formulations. The best formulations of microspheres and nanoparticles, based on greater drug release, drug entrapment, and compatibility characteristics, were attributed to the study of drug permeation by non-everted intestinal sacs, in vivo anti-hyperglycemic activity, and in vitro anticancer activity.
CONCLUSION: This study suggests that the proposed metformin HCl formulation can dramatically reduce hyperglycemic conditions and may also have anticancer potential.
MATERIALS AND METHODS: K. odoratissima methanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated.
RESULTS: Our results demonstrated that K. odoratissima has an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2.
CONCLUSION: This study demonstrated that K. odoratissima exhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.
METHODS: We established an in vitro OA culture model by exposing human chondrocytes to proinflammatory cytokine and interleukin (IL)-1β for 36 hours prior to treatment with the herbals: C. quadrangularis, W. somnifera, and the combination of the two herbals. Cell viability, toxicity, and gene expression of OA modifying agents were examined. In addition, expression of survivin, which is crucial for cell growth, was analyzed. In vivo work on osteotomized rats studied the bone and cartilage regenerative effects of C. quadrangularis, W. somnifera, and the combination therapy.
RESULTS: Exposure of chondrocytes to IL-1β induced significant toxicity and cell death. However, herbal treatment alleviated IL-1β induced cell toxicity and upregulated cell growth and proliferation. C. quadrangularis inhibited gene expression of cytokines and matrix metalloproteinases, known to aggravate cartilage and bone destruction, and augmented expression of survivin by inhibiting p38 MAPK. Interestingly, osteotomized rats treated with C. quadrangularis drastically enhanced alkaline phosphatase and cartilage tissue formation as compared to untreated, W. somnifera only, or the combination of both herbals.
CONCLUSION: Our findings demonstrate for the first time the signaling mechanisms regulated by C. quadrangularis and W. somnifera in OA and osteogenesis. We suggest that the chondroprotective effects and regenerative ability of these herbals are via the upregulation of survivin that exerts inhibitory effects on the p38 MAPK signaling pathway. These findings thus validate C. quadrangularis as a potential therapeutic for rheumatic disorders.
Materials and methods: The antiproliferative activity of koenimbin was examined using MTT, and the apoptotic detection was carried out by acridine orange/propidium iodide (AO/PI) double-staining and multiparametric high-content screening (HCS) assays. Caspase bioluminescence assay, reverse transcription polymerase chain reaction (RT-PCR), and immunoblotting were conducted to confirm the expression of apoptotic-associated proteins. Cell cycle analysis was investigated using flow cytometry. Involvement of nuclear factor-kappa B (NF-κB) was analyzed using HCS assay. Aldefluor™ and prostasphere formation examinations were used to evaluate the impact of koenimbin on PC-3 CSCs in vitro.
Results: Koenimbin remarkably inhibited cell proliferation in a dose-dependent manner. Koenimbin induced nuclear condensation, formation of apoptotic bodies, and G0/G1 phase arrest of PC-3 cells. Koenimbin triggered the activation of caspase-3/7 and caspase-9 and the release of cytochrome c, decreased anti-apoptotic Bcl-2 and HSP70 proteins, increased pro-apoptotic Bax proteins, and inhibited NF-κB translocation from the cytoplasm to the nucleus, leading to the activation of the intrinsic apoptotic pathway. Koenimbin significantly (P<0.05) reduced the aldehyde dehydrogenase-positive cell population of PC-3 CSCs and the size and number of PC-3 CSCs in primary, secondary, and tertiary prostaspheres in vitro.
Conclusion: Koenimbin has chemotherapeutic potential that may be employed for future treatment through decreasing the recurrence of cancer, resulting in the improvement of cancer management strategies and patient survival.