Aging phenotype in AD brain organoids: Track to success and challenges.

Alzheimer's disease (AD) poses a complex challenge, with abnormal protein accumulation in the brain causing memory loss and cognitive decline. Traditional models fall short in AD research, prompting interest in 3D brain organoids (BOs) from human stem cells. These findings hold promise for unveiling the mechanisms of AD, especially in relation to aging. However, an understanding of the aging impact of AD remains elusive. BOs offer insight but face challenges. This review delves into the role of BOs in deciphering aging-related AD and acknowledges limitations. Strategies to enhance BOs for accurate aging modeling in AD brains are suggested. Strengthened by molecular advancements, BOs have the potential to uncover the aging phenotype, advancing AD research.

Anti-inflammatory activity of d-pinitol possibly through inhibiting COX-2 enzyme: in vivo and in silico studies.

Introduction: D-pinitol, a naturally occurring inositol, has diverse biological activities like antioxidant, antimicrobial and anticancer activities. This study aimed to evaluate anti-inflammatory effect of d-pinitol in a chick model. Additionally, in silico studies were performed to evaluate the molecular interactions with cyclooxygenase-2 (COX-2). Methods: The tested groups received d-pinitol (12.5, 25, and 50 mg/kg) and the standard drugs celecoxib and ketoprofen (42 mg/kg) via oral gavage prior to formalin injection. Then, the number of licks was counted for the first 10 min, and the paw edema diameter was measured at 60, 90, and 120 min. Results and Discussion: The d-pinitol groups significantly (p < 0.05) reduced the number of paw licks and paw edema diameters, compared to negative control. When d-pinitol was combined with celecoxib, it reduced inflammatory parameters more effectively than the individual groups. The in silico study showed a promising binding capacity of d-pinitol with COX-2. Taken together, d-pinitol exerted anti-inflammatory effects in a dose-dependent manner, possibly through COX-2 interaction pathway.

Antiemetic effects of sclareol, possibly through 5-HT3 and D2 receptor interaction pathways: In-vivo and in-silico studies.

BACKGROUND: Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and movement. Nevertheless, preventing emesis during chemotherapy or other situations is a significant issue for researchers. Hence, the majority view contends that successfully combining therapy is the best course of action. In-vivo analysis offers a more comprehensive grasp of how compounds behave within a complex biological environment, whereas in-silico evaluation refers to the use of computational models to forecast biological interactions. OBJECTIVES: The objectives of the present study were to evaluate the effects of Sclareol (SCL) on copper sulphate-induced emetic chicks and to investigate the combined effects of these compounds using a conventional co-treatment approach and in-silico study. METHODS: SCL (5, 10, and 15 mg/kg) administered orally with or without pre-treatment with anti-emetic drugs (Ondansetron (ODN): 24 mg/kg, Domperidone (DOM): 80 mg/kg, Hyoscine butylbromide (HYS): 100 mg/kg, and Promethazine hydrochloride (PRO): 100 mg/kg) to illustrate the effects and the potential involvement with 5HT3, D2, M3/AChM, H1, or NK1 receptors by SCL. Furthermore, an in-silico analysis was conducted to forecast the role of these receptors in the emetic process. RESULTS: The results suggest that SCL exerted a dose-dependent anti-emetic effect on the chicks. Pretreatment with SCL-10 significantly minimized the number of retches and lengthened the emesis tendency of the experimental animals. SCL-10 significantly increased the anti-emetic effects of ODN and DOM. However, compared to the ODN-treated group, (SCL-10 + ODN) group considerably (p < 0.0001) extended the latency duration (109.40 ± 1.03 s) and significantly (p < 0.01) decreased the number of retches (20.00 ± 0.70), indicating an anti-emetic effect on the test animals. In in-silico analysis, SCL exhibited promising binding affinities with suggesting receptors. CONCLUSION: SCL-10 exerted an inhibitory-like effect on emetic chicks, probably through the interaction of the 5HT3 and D2 receptors. Further studies are highly appreciated to validate this study and determine the precise mechanism(s) behind the anti-emetic effects of SCL. We expect that SCL-10 may be utilized as an antiemetic treatment in a single dosage form or that it may function as a synergist with other traditional medicines.

Antioxidant, antibacterial, antidiarrheal and antipyretic activities of organic crude fractions of Commelina paludosa.

BACKGROUND: The herb, Commelina paludosa (CP) Blume (Family-Commelinaceae) is medicinally used by the traditional practitioners in Bangladesh. However, there is a lack of scientific evidence on this medicinal herb. AIM AND OBJECTIVES: This study aimed to evaluate the phytochemical and pharmacological activities of CP (ethanol [ECP], chloroform [CCP] and n-hexane [NHCP] of whole-plant extracts). MATERIALS AND METHODS: For this antioxidant, antimicrobial, antidiarrheal and antipyretic activities of crude extracts of CP were conducted by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging, disc diffusion and serial dilution, castor oil-induced diarrhea and yeast powder-induced pyrexia methods respectively. RESULTS AND OBSERVATION: The results suggest that all the fractions significantly scavenged DPPH radicals. In the disc diffusion test, the zones of inhibition were observed within the range of 7 mm to 30.67 mm at 500 mg/disc. The highest zones of inhibition were observed by ECP, CCP and NHCP against Bacillus azotoformans, Lactobacillus coryifomis and Salmonella typhi respectively. NHCP was found to exert stronger antibacterial effect than the ECP and CCP. CONCLUSION: Minimum inhibitory concentrations were detected within the range of 31.25 and 250 µg/ml. Moreover, the crude fractions also showed significant (P < 0.05) antidiarrheal and antipyretic activities in Swiss mice. CP may be a good source of therapeutic components.