ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (BM) is commonly employed in the Indian traditional system of medicines, i.e. Ayurveda as a memory booster, antioxidant, anti-inflammatory, antipyretic, analgesic, sedative and anti-epileptic for decades. AIM OF THE STUDY: To evaluate the neuroprotective effect of Bacopa monnieri (BM) in experimental model of autism spectrum disorder (ASD) in Wistar rats and explore its mechanism of action. MATERIALS AND METHODS: BacoMind, was evaluated for its neuroprotective effect in valproic acid (VPA) model of ASD. For in-vivo study, the pregnant female Wistar rats were divided in two groups; normal control (NC) and VPA group who received single dose of normal saline (0.9%) or 600 mg/kg dose of VPA respectively on gestation day (G.D) 12.5. After the birth, all pups were segregated according to the sex. All the male pups from the dams were divided into six groups: Group 1 (NC, treated with only 0.9% normal saline, group 2 (VPA, treated 600 mg/kg on G.D12.5 and normal saline from post natal day (PND) 23 to 43), group 3 (risperidone 2.5 mg/kg, PND 23 to 43) and groups 4, 5 and 6 (BM 20, 40, 80 mg/kg, PND 23 to 43). All experimental groups were subjected to batteries of behavior parameters (three chamber sociability test, Morris Water Maze, elevated plus maze, open field and rota rod test), biochemical parameters such as oxidative stress (GSH, SOD, Catalase, MDA), inflammatory cytokines (Il-1ß, IL-6, IL-10, TNF-α), histopathological examination (cresyl violet staining) of hippocampus (HC) and prefrontal cortex (PFC) regions. Further, the mRNA as well as protein expression of AMPA receptor was evaluated using RT-PCR and western blot respectively to study the mechanism of neuroprotective effect of BM. The in-silico analysis followed evaluating the binding profile of different constituents of BacoMind with AMPA receptor. RESULTS: The results of the in-vivo study indicated BM at 80 mg/kg ameliorated abnormal behavioral paradigms such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination exhibited by the VPA model of ASD in rats. Furthermore, BM was found to have a significant anti-oxidant (increasing GSH, SOD, and catalase and decreasing MDA levels) and anti-inflammatory properties (decreasing IL-1ß, 6, TNF- α). The histopathological score was also found to be significantly improved by BM in a dose dependent manner in both HC and PFC. In addition to this, the up-regulated mRNA as well as protein expression of AMPA receptor was significantly reduced by 80 mg/kg dose of BM in both HC and PFC. Further, the in-silico analysis of different constituents of BacoMind with AMPA receptor demonstrated that luteolin and apigenin showed good binding to both the competitive antagonist binding site, non-competitive antagonist binding site and allosteric modulator site while Bacosaponin C showed good binding to the non-competitive antagonist binding site. CONCLUSION: The present study concluded that BM can be a potential candidate for ameliorating the ASD symptoms in rats and acts via modulating the up-regulated AMPA receptor expression.
Subject(s)
Autism Spectrum Disorder , Bacopa , Neuroprotective Agents , Prenatal Exposure Delayed Effects , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/drug therapy , Bacopa/chemistry , Catalase , Disease Models, Animal , Female , Humans , Male , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Pregnancy , RNA, Messenger , Rats , Rats, Wistar , Receptors, AMPA , Saline Solution , Superoxide Dismutase , Valproic Acid/pharmacologyABSTRACT
Purpose:@#The technology of 3D printing (3DP) exists for quite some time, but it is still not utilized to its full potential in the field of orthopaedics and traumatology, such as underestimating its worth in virtual preoperative planning (VPP) and designing various models, templates, and jigs. It can be a significant tool in the reduction of surgical morbidity and better surgical outcome avoiding various associated complications.@*Methods:@#An observational study was done including 91 cases of complex trauma presented in our institution requiring operative fixation. Virtual preoperative planning and 3DP were used in the management of these fractures. Surgeons managing these cases were given a set of questionnaire and responses were recorded and assessed as a quantitative data.@*Results:@#In all the 91 cases, where VPP and 3DP were used, the surgeons were satisfied with the outcome which they got intraoperatively and postoperatively. Surgical time was reduced, with a better outcome. Three dimensional models of complex fracture were helpful in understanding the anatomy and sketching out the plans for optimum reduction and fixation. The average score of the questionnaire was 4.5, out of a maximum of 6, suggesting a positive role of 3DP in orthopaedics.@*Conclusion:@#3DP is useful in complex trauma management by accurate reduction and placement of implants, reduction of surgical time and with a better outcome. Although there is an initial learning curve to understand and execute the VPP and 3DP, these become easier with practice and experience.
