Effect of Centella asiatica ethanol extract on zebrafish larvae ( Danio rerio) insomnia model through inhibition of Orexin, ERK, Akt and p38.

Background: Insomnia is difficulty initiating or maintaining sleep for at least three nights a week or more and lasting for at least 3 months. One of the molecules that play a role in the circadian rhythm of arousal system is hypocretin/orexin. Orexin activates the p38-MAPK signaling pathway and increases phosphorylated ERK1/2 levels. Centella asiatica (CA) has a role in the signal work of the MAPK/ERK, Akt, and p38 path in many various diseases. Methods: The research method used is true laboratory experimental. The research approach used was randomized control group post-test only. Zebrafish embryos aged 0-7 dpf were used in this study. The treatment group consisted of 5 groups: normal, insomnia, insomnia + 2.5 µg/mL CA, insomnia + 5 µg/mL CA, and insomnia + 10 µg/mL CA. The locomotor motion of zebrafish larvae was observed using Basler cameras on days five-, six- and seven-day post fertilization (dpf), then analyzed by using Western Blot method. Results: The results proved that exposure to CA extract was able to reduce the expression of orexin (91963 ± 9129) and p38 (117425 ± 6398) as an arousal trigger in the sleep-wake cycle, with the most optimal concentration of CA 5 µg/mL. Exposure to CA extract was also able to reduce the expression of ERK (94795 ± 30830) and Akt (60113.5 ± 27833.5) with an optimum concentration of CA 2.5 µg/mL. Conclusion: Exposure to CA extract was able to improve the sleep activity of zebrafish larvae insomnia model by extending the total inactivity time ( cumulative duration) and shortening the duration of first sleep ( latency to first) in light and dark phases through inhibition of orexin, ERK, p38, and Akt.

Bifidobacterium longum Administration Diminishes Parasitemia and Inflammation During Plasmodium berghei Infection in Mice.

Purpose: During Plasmodium berghei (P. berghei) infection, infected erythrocytes are sequestered in gut tissues through microvascular circulation, leading to dysbiosis. This study aimed to investigate the effect of Lactobacillus casei (L. casei) and Bifidobacterium longum (B. longum) administration on the parasitemia level, gut microbiota composition, expression of cluster of differentiation 103 (CD103) in intestinal dendritic and T regulatory cells (T reg), plasma interferon gamma (IFN-γ) and tumor necrosis factor (TNF-α) levels in P. berghei infected mice. Methods: P. berghei was inoculated intraperitoneally. Infected mice were randomly divided into 5 groups and treated with either L. casei, B. longum, or the combination of both for 5 days before up to 6 days post-infection (p.i). The control group was treated with phosphate-buffered saline (PBS), while uninfected mice were used as negative control. Levels of CD103 and forkhead box P3 (FoxP3) expression were measured by direct immunofluorescense, while plasma IFN-γ and TNF-α level were determined using enzyme-linked immunosorbent assay (ELISA). Results: All treated groups showed an increase in parasitemia from day 2 to day 6 p.i, which was significant at day 2 p.i (p = 0.001), with the group receiving B. longum displaying the lowest degree of parasitemia. Significant reduction in plasma IFN-γ and TNF-α levels was observed in the group receiving B. longum (p = 0.022 and p = 0.026, respectively). The CD103 and FoxP3 expression was highest in the group receiving B. longum (p = 0.01 and p = 0.02, respectively). Conclusion: B. longum showed the best protective effect against Plasmodium infection by reducing the degree of parasitemia and modulating the gut immunity. This provides a basis for further research involving probiotic supplementation in immunity modulation of infectious diseases.

Vertigo due to cerebellar cavernous malformation: A case report.

Central vertigo is a result of vestibular structure dysfunction in the central nervous system. Currently, misdiagnoses between peripheral and central lesions are frequent, and diagnostic testing costs are high. Identifying the characteristics of these 2 conditions is challenging. We can provide better treatment if we can establish a diagnosis earlier. Cerebral cavernous malformation (CCM) at the cerebellum is a cerebellar lesion that causes symptoms of central vertigo. We report a patient, 20th years old, female, with vertigo for 1 month before being admitted. Vertigo was getting worse, and when the patient arrived at our hospital, vertigo was accompanied by headache, right and left abducens nerve palsy, horizontal nystagmus bidirectional, vertical nystagmus, and weakness on the right side of the body. A brain magnetic resonance imaging (MRI) was performed before surgery and shows a lesion suggestive of CCM at the cerebellum with a hemorrhagic component inside and non-communicating hydrocephalus. There is no vascular malformation based on digital subtraction angiography result. MRI is the most sensitive and specific modality for detecting CCM, whereas cerebral angiography rarely detects this malformation. The patient got surgical treatment, with suboccipital decompression procedures and CCM excision. The histopathological results after surgical treatment revealed a cerebral cavernous malformation. Vertigo, headache, double vision, and weakness on the right side of the body were resolved after surgery.