Ocimum sanctum Alters the Lipid Landscape of the Brain Cortex and Plasma to Ameliorate the Effect of Photothrombotic Stroke in a Mouse Model.

Stroke-like injuries in the brain result in not only cell death at the site of the injury but also other detrimental structural and molecular changes in regions around the stroke. A stroke-induced alteration in the lipid profile interferes with neuronal functions such as neurotransmission. Preventing these unfavorable changes is important for recovery. Ocimum sanctum (Tulsi extract) is known to have anti-inflammatory and neuroprotective properties. It is possible that Tulsi imparts a neuroprotective effect through the lipophilic transfer of active ingredients into the brain. Hence, we examined alterations in the lipid profile in the cerebral cortex as well as the plasma of mice with a photothrombotic-ischemic-stroke-like injury following the administration of a Tulsi extract. It is also possible that the lipids present in the Tulsi extract could contribute to the lipophilic transfer of active ingredients into the brain. Therefore, to identify the major lipid species in the Tulsi extract, we performed metabolomic and untargeted lipidomic analyses on the Tulsi extract. The presence of 39 molecular lipid species was detected in the Tulsi extract. We then examined the effect of a treatment using the Tulsi extract on the untargeted lipidomic profile of the brain and plasma following photothrombotic ischemic stroke in a mouse model. Mice of the C57Bl/6j strain, aged 2-3 months, were randomly divided into four groups: (i) Sham, (ii) Lesion, (iii) Lesion plus Tulsi, and (iv) Lesion plus Ibuprofen. The cerebral cortex of the lesioned hemisphere of the brain and plasma samples were collected for untargeted lipidomic profiling using a Q-Exactive Mass Spectrometer. Our results documented significant alterations in major lipid groups, including PE, PC, neutral glycerolipids, PS, and P-glycerol, in the brain and plasma samples from the photothrombotic stroke mice following their treatment with Tulsi. Upon further comparison between the different study groups of mice, levels of MGDG (36:4), which may assist in recovery, were found to be increased in the brain cortexes of the mice treated with Tulsi when compared to the other groups (p < 0.05). Lipid species such as PS, PE, LPG, and PI were commonly altered in the Sham and Lesion plus Tulsi groups. The brain samples from the Sham group were specifically enriched in many species of glycerol lipids and had reduced PE species, while their plasma samples showed altered PE and PS species when compared to the Lesion group. LPC (16:1) was found in the Tulsi extract and was significantly increased in the brains of the PTL-plus-Tulsi-treated group. Our results suggest that the neuroprotective effect of Tulsi on cerebral ischemia may be partially associated with its ability to regulate brain and plasma lipids, and these results may help provide critical insights into therapeutic options for cerebral ischemia or brain lesions.

Analysis of fluoro based pyrazole analogues as a potential therapeutics candidate against Japanese encephalitis virus infection.

Japanese encephalitis virus (JEV) is the leading causative agent of encephalitis and its associated mortality among children. JEV modulates host cell machinery for its advantage, such as oxidative damage which subsequently leads to stress responsive pathways. The present study analyzes new series of dinitroaryl substituted derivatives (1a-1f), containing pyrazole moiety and explores its potential ensuing anti-JEV activity. Out of all synthesized derivatives, compounds 1b and 1f were selected based on minimal cytotoxicity. In vitro inhibition of more than 70% and 90% were observed with compounds 1b and 1f, respectively, in neuronal cells. Dose-response analyses highlighted 1f exhibiting better antiviral activity than 1b. The mice treated with compound 1b or 1f did not show any noticeable toxicity at a dose of 100mg/kg/day when administered intraperitoneally till 96th h. Inhibition of up to 41% and 70% JEV mRNA in spleen and 33% to 43% in brain tissue was observed with compounds 1b and 1f, respectively. Both the compounds suppressed JEV induced ROS generation by up-regulating the NQO1 and HO-1 proteins. Our result suggests the interlocked positive feedback loops of NRF2-SQSTM1 signaling pathway to be regulated by the synthesized compounds. The potential of these compounds can be further tested for broad-spectrum antiviral effects with other flaviviruses in the path towards the development of therapeutics.

Ocimum sanctum [Tulsi] as a Potential Immunomodulator for the Treatment of Ischemic Injury in the Brain.

Stroke causes brain damage and is one of the main reasons for death. Most survivors of stroke face long-term physical disabilities and cognitive dysfunctions. In addition, they also have persistent emotional and behavioral changes. The two main treatments that are effective are reperfusion with recombinant tissue plasminogen activator and recanalization of penumbra using mechanical thrombectomy. However, these treatments are suitable only for a few patients due to limitations such as susceptibility to hemorrhage and the requirement for administering tissue plasminogen activators within the short therapeutic window during the early hours following a stroke. The paucity of interventions and treatments could be because of the multiple pathological mechanisms induced in the brain by stroke. The ongoing immune response following stroke has been attributed to the worsening brain injury. Hence, novel compounds with immunomodulatory properties that could improve the outcome of stroke patients are required. Natural compounds and medicinal herbs with anti-inflammatory activities and having minimal or no adverse systemic effect could be beneficial in treating stroke. Ocimum sanctum is a medicinal herb that can be considered an effective therapeutic option for ischemic brain injury. Ocimum sanctum, commonly known as holy basil or "Tulsi," is mentioned as the "Elixir of Life" for its healing powers. Since antiquity, Tulsi has been used in the Ayurvedic and Siddha medical systems to treat several diseases; it possesses immuno-modulatory activity, which can alter cellular and humoral immune responses. Tulsi can be considered a potential option as an immuno-modulator for treating various diseases, including brain stroke. In this review, we will focus on the immunomodulatory properties of Tulsi, specifically its effect on both innate and adaptive immunity, as well as its antioxidant and anti-inflammatory properties, which could potentially be effective in treating ongoing immune reactions following ischemic brain injury.

Surgical repair of indirect inguinal hernia in bonnet macaque (Macaca radiata).

Background: Hernia is a protrusion of an organ from the wall of the cavity bearing it. Omentum, adipose tissue, and intestinal loops are the most frequently involved organs. The present case report is a rare case of indirect inguinal hernia having omentum engaged in scrotum through hernial ring in a bonnet macaque (Macaca radiata) and its surgical management. Case Description: A 19-year-old male bonnet macaque was presented with distension of the right inguinal and scrotal region. Physical examination revealed an inguinal hernia. Surgical intervention was deemed necessary considering the state of the animal. The herniation was surgically corrected by the removal of the protruded fatty mass. The monkey was kept in strict confinement till complete healing. The animal recovered uneventfully in 2 weeks without any post-operative complications. This case report details a successful surgical repair of an indirect inguinal hernia in a bonnet macaque. Conclusion: Based on the present case study, it is concluded that surgery can be an ideal and effective option for the treatment of inguinal hernias in primates.

Reproductive performance of genetically engineered mice housed in different housing systems.

The genetically engineered mice require special husbandry care and are mainly housed in Individually Ventilated Cage (IVC) systems and Static Micro Isolator Cages (SMIC) to minimize the risk for spreading undesirable microorganisms. However, the static micro isolation cage housing like SMIC are being replaced with IVC systems in many facilities due to a number of benefits like a higher density housing in limited space, better protection from biohazards and allergens and decreased work load due to decreased frequency of cage changing required in this system. The purpose of this study was to examine the reproductive performance of genetically engineered mice housed in individually ventilated cages (IVC) and Static Micro Isolator Cages (SMIC). When the B6C3-Tg (APPswe, PSEN1dE9) 85Dbo/Mmjax transgenic mice were housed in these two housing systems, the number of litters per dam, number of pups born per dam and number of pups weaned per dam were found to be slightly higher in the IVC as compared to the SMIC but the difference was not significant (P<0.05). In case of Growth Associated Protein 43 (GAP-43) knockout mice, the number of litters born per dam and the number of pups born per dam were marginally higher in the IVC as compared to those housed in SMIC but the difference was not significant (P<0.05). Only the number of pups weaned per dam were found to be significantly higher as compared to those housed in the SMIC system at P<0.05.