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Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski’s rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future.

Background:Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as “Sinatha,” and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds.Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds.Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01).Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.

Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein’s anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder that usually includes both obsessions and compulsions. Morinda citrifolia L. (Noni) is a functional food and it is a well-known plant due to its potential therapeutic effects on human health in many disorders including neurological and neurodegenerative diseases. The purpose of this study was to evaluate the potential effect of M. citrifolia fruits extract (MCFE) against obsessive-compulsive disorder using the marble burying and nestlet shredding behavior mice models. In addition, brain neurotransmitters such as dopamine (DA), serotonin and noradrenaline (NA) were also assessed. Five mice were placed in each of the different groups, and the treatment was given to the animals for a period of 15 days. The marble burying test was evaluated for 30 min on days 1, 7, and 14 while the nestlet shredding test was evaluated for 60 min on days 2, 8, and 15. Treatments with MCFE (100 and 200 mg/kg, p.o.) significantly improved in both behavior tasks when compared to the control group. In addition, diazepam (2 mg/kg, i.p.) and fluoxetine (15 mg/kg, p.o.) were also significantly improved in both tasks when compared with the control mice. Further locomotor activity study revealed that MCFE and fluoxetine did not affect the locomotor functions when compared to vehicle treated mice. In contrast, diazepam significantly decreased locomotion when compared to the control group. The significant amelioration of biogenic amines were observed in the MCFE-treated animals with increased serotonin levels. The histopathology of the brain, liver, and kidney tissues after MCFE administration revealed normal morphological structure with no signs of toxicity or abnormalities. All these results together suggest that MCFE can be a potential drug candidate for the treatment of OCD. Future research should focus on theidentification and the anti-compulsive activity of the constituents from M. citrifolia.

The rate of breast cancer is rapidly increasing and discovering medications with therapeutic effects play a significant role in women’s health. Drugs derived from marine sponges have recently received FDA approval for the treatment of malignant tumors, including metastatic breast cancer. Spirastrella pachyspira (marine sponge) is mainly obtained from the western coastal region of India, and its anticancer potential has not been explored. Hence, the present study aimed to evaluate the anticancer potential of Spirastrella pachyspira extracts and its bioactive molecule sphingosine. The extracts were prepared using hexane, chloroform, ethyl acetate, and ethanol. The cytotoxic potential of the extracts were determined by an in-vitro MTT assay using SK-BR-3 cancer cell line. Subsequently, acute toxicity investigation was conducted in Swiss albino mice. Then, the anticancer effects of the extract was investigated in a xenograft model of SK-BR-3 caused breast cancer. DAPI staining was used to assess the extract’s ability to induce apoptosis. In addition, in-silico study was conducted on sphingosine with extracellular site of HER2. The ethyl acetate extract of Spirastrella pachyspira (IC50: 0.04 µg/ml) showed comparable anticancer effects with standard doxorubicin (IC50: 0.054 µg/ml). The LD50 of the extracts in acute toxicity testing was fund to be 2000 mg/kg b.wt. The survival index of mice in ethanol extract was 83.33%, whereas that of standard doxirubicin was 100%, indicating that ethyl acetate extract Spirastrella pachyspira has good antiproliferative/cytotoxic properties. The results were well comparable with standard doxorubicin. Further, the docking studies of sphingosine against HER2 demonstrated that the bioactive molecule engage with the extracellular region of HER2 and block the protein as also shown by standard trastuzumab. The findings of this research suggest that Spirastrella pachyspira and sphingosine may be potential candidate for the treatments of breast cancer, particularly for HER2 positive cells. Overall, the present results demonstrate that sphingosine looks like a promising molecule for the development of new drugs for the treatment of cancer. However, in order to carefully define the sphingosine risk-benefit ratio, future research should focus on evaluating in-vivo and clinical anticancer studies. This will involve balancing both their broad-spectrum effectiveness and their toxicity.