In silico analysis of quranic and prophetic medicinals plants for the treatment of infectious viral diseases including corona virus.

Coronavirus disease (COVID-19) is an infection of the respiratory system caused by single standard RNA viruses named as Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). The disease appeared as a serious problem and the leading cause of death in human beings throughout the world. The main source of different phytochemicals are plants, which helps in the development of new drugs against various ailments. Islam is comprehensive religion and a complete code of life for Muslims. The teaching of Islam, according to the Holy Quran and Hadith are universal for the benefit of humanity. Islam believes that every ailment is from God and who made the disease definitely made its medication. There is a complete guideline with regard to taking measures against infectious diseases such as quarantine and seeking medicinal treatment. The research objective is to gather the knowledge of medicinal plants described in the Holy Quran or utilized by the Prophet (SAW) for the treatment of different ailments or advised to use them to boost immunity and strengthen the body. Scientists across the globe have found these plants beneficial for many diseases and have antiviral potential. In present study, the six plant species including Olea europaea, Nigella sativa, Allium Sativum, Allium cepa, Zingiber officinale and Cassia senna were selected which contain phytochemicals like Calcium Elenolate, Thymoquinone, S-Allylcysteine, Dipropyl Disulfide, Sesquiterpene, Monoterpene, Pelargonidin 3-Galactoside ion and Kaempferol. The phytochemicals monoterpene (from Zingiber officinale) shows best interaction with target proteins RdRP, 3CLPro, ACE2. Calcium Elonate (from olive) bonds with 3CLPro, ACE2 and Kemoferol and Pelargomidine (from Senna Makki) bonds with RdRP, ACE2. The ligands show a unique set of intersections i.e. hydrogen bonding, and alkyl interaction. These medicinal plants can be utilized immediately for the treatment of COVID-19 as their safety is already established. This treatment can enhance recovery when combined with other treatments. Furthermore, the screening of bioactive compounds or phytochemicals found in these plants can be utilized to design new therapeutic drug to treat COVID-19 pandemic.

Molecular Mechanisms of Anticancer Activities of Puerarin.

Medicinal plants are a vital source of natural products (NPs) that can cure cancer through modulation of different pathways, including oxidative stress, extrinsic and intrinsic apoptosis, cell cycle, inflammation, NF-kB, PI3K/AKT/mTOR, AMPK (JNK), MEK/ERK (Raf)-MEK-ERK and autophagy. Puerarin (Pue), an important NP belonging to the isoflavone glycoside group, is derived from Pueraria lobata (Willd.) Ohwi, Pueraria thomsonii Benth, and Pueraria tuberosa (Willd.). This NP was approved by the Chinese Ministry of Health for the treatment of different diseases in 1993, but it was also later reported to exhibit anticancer activity. Pue causes cancer cells death through modulation of different mechanisms including oxidative stress, intrinsic and extrinsic, Survivin and XIAP, PI3K/AKT/mTOR, Ras-Raf-MEK-ERK, JNK, cell cycle, AMPK, NF-kB, inflammation and autophagy pathways. Therefore, this review compiles for the first time the studies about the anticancer mechanism of Pue and provides comprehensive information about the anticancer effects of Pue. This review may serve as a basis for future research and clinical treatment.

Impact of chronically alternating light-dark cycles on circadian clock mediated expression of cancer (glioma)-related genes in the brain.

Disruption of the circadian rhythm is a risk factor for cancer, while glioma is a leading contributor to mortality worldwide. Substantial efforts are being undertaken to decrypt underlying molecular pathways. Our understanding of the mechanisms through which disrupted circadian rhythm induces glioma development and progression is incomplete. We, therefore, examined changes in the expression of glioma-related genes in the mouse brain after chronic jetlag (CJL) exposure. A total of 22 candidate tumor suppressor (n= 14) and oncogenes (n= 8) were identified and analyzed for their interaction with clock genes. Both the control and CJL groups were investigated for the expression of candidate genes in the nucleus accumbens, hippocampus, prefrontal cortex, hypothalamus, and striatum of wild type, Bmal1-/- and Cry1/2 double knockout male mice. We found significant variations in the expression of candidate tumor suppressor and oncogenes in the brain tissues after CJL treatment in the wild type, Bmal1-/- and Cry1/2 double knockout mice. In response to CJL treatment, some of the genes were regulated in the wild type, Bmal1-/- and Cry1/2 similarly. However, the expression of some of the genes indicated their association with the functional clock. Overall, our result suggests a link between CJL and gliomas risk at least partially dependent on the circadian clock. However, further studies are needed to investigate the molecular mechanism associated with CJL and gliomas.

Relative importance of proteinase-activated receptor-1 versus matrix metalloproteinases in intracerebral hemorrhage-mediated neurotoxicity in mice.

BACKGROUND AND PURPOSE: To reduce bleeding and damage to central nervous system tissue in intracerebral hemorrhage, the coagulant effect of thrombin is essential. However, thrombin itself can kill neurons in intracerebral hemorrhage as can the matrix metalloproteinases (MMPs), which are also elevated in this condition, in part due to thrombin-mediated activation of MMPs. It is thus important to understand and block the neurotoxic effects of thrombin without inhibiting its therapeutic outcomes. In this study, we have investigated the relative roles of proteinase activated receptor-1, a thrombin receptor, and MMPs in brain injury induced by thrombin or blood. METHODS: Mice were subjected to stereotactic intracerebral injections of saline, thrombin, and autologous blood, with or without hirudin, a thrombin inhibitor, or GM6001, an MMP inhibitor. Twenty-four hours later, tissue sections were obtained to evaluate the area of brain damage and extent of dying neurons. Data from wild-type mice were compared with results obtained with proteinase activated receptor-1 null mice. RESULTS: In blood-induced damage to the brain parenchyma, both hirudin and GM6001 significantly reduced injury to a comparable extent (>40%) implicating both thrombin and MMPs in neurotoxicity. In proteinase activated receptor-1 null mice, blood-induced brain damage was reduced by 22.6% relative to wild-type animals; by comparison, the blood-induced brain damage was reduced by 48.3% using GM6001. CONCLUSIONS: The neurotoxicity of blood in intracerebral hemorrhage involves both proteinase activated receptor-1 and MMP activation, with the latter appearing more prominent in causing death.

Persistent motor deficit following infusion of autologous blood into the periventricular region of neonatal rats.

Periventricular hemorrhage (PVH) in the brain of premature infants is often associated with developmental delay and persistent motor deficits. Our goal is to develop a rodent model that mimics the behavioral phenotype. We hypothesized that autologous blood infusion into the periventricular germinal matrix region of neonatal rats would lead to immediate and long-term behavioral changes. Tail blood or saline was infused into the periventricular region of 1-day-old rats. Magnetic resonance (MR) imaging was used to demonstrate the hematoma. Rats with blood infusion, as well as saline and intact controls, underwent behavior tests until 10 weeks age. Blood-infused rats displayed significant delay in motor development (ambulation, righting response, and negative geotaxis) to 22 days of age. As young adults, they exhibited impaired ability to stay on a rotating rod and to reach for food pellets. MR imaging at 10 weeks demonstrated subsets of rats with normal appearing brains, focal cortical infarcts, or mild hydrocephalus. There was a good correlation between MR imaging and histological findings. Some rats exhibited periventricular heterotopia and/or subtle striatal abnormalities not apparent on MR images. We conclude that autologous blood infusion into the brain of neonatal rats successfully models some aspects of periventricular hemorrhage that occurs after premature birth in humans.