Liver injury induced by drugs has become a primary reason for acute liver disease and therefore posed a potential regulatory and clinical challenge over the past few decades and has gained much ...attention. It also remains the most common cause of failure of drugs during clinical trials. In 50% of all acute liver failure cases, drug-induced hepatoxicity is the primary factor and 5% of all hospital admissions.
The various hepatotoxins used to induce hepatotoxicity in experimental animals include paracetamol, CCl4, isoniazid, thioacetamide, erythromycin, diclofenac, alcohol, etc. Among the various models used to induce hepatotoxicity in rats, every hepatotoxin causes toxicity by different mechanisms.
The drug-induced hepatotoxicity caused by paracetamol accounts for 39% of the cases and 13% hepatotoxicity is triggered by other hepatotoxic inducing agents.
Research carried out and the published papers revealed that hepatotoxins such as paracetamol and carbon- tetrachloride are widely used for experimental induction of hepatotoxicity in rats.
Neurodegenerative disorders are commonly erratic influenced by various factors including lifestyle, environmental, and genetic factors. In recent observations, it has been hypothesized that exposure ...to various environmental factors enhances the risk of Alzheimer’s disease (AD). The exact etiology of Alzheimer’s disease is still unclear; however, the contribution of environmental factors in the pathology of AD is widely acknowledged. Based on the available literature, the review aims to culminate in the prospective correlation between the various environmental factors and AD. The prolonged exposure to the various well-known environmental factors including heavy metals, air pollutants (particulate matter), pesticides, nanoparticles containing metals, industrial chemicals results in accelerating the progression of AD. Common mechanisms have been documented in the field of environmental contaminants for enhancing amyloid-β (Aβ) peptide along with tau phosphorylation, resulting in the initiation of senile plaques and neurofibrillary tangles, which results in the death of neurons. This review offers a compilation of available data to support the long-suspected correlation between environmental risk factors and AD pathology.
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Advances in next-generation sequencing technologies have accelerated the momentum of metagenomic studies, which is increasing yearly. The metagenomics field is one of the versatile applications in ...microbiology, where any interaction in the environment involving microorganisms can be the topic of study. Due to this versatility, the number of applications of this omics technology reached its horizons. Agriculture is a crucial sector involving crop plants and microorganisms interacting together. Hence, studying these interactions through the lenses of metagenomics would completely disclose a new meaning to crop health and development. The rhizosphere is an essential reservoir of the microbial community for agricultural soil. Hence, we focus on the R&D of metagenomic studies on the rhizosphere of crops such as rice, wheat, legumes, chickpea, and sorghum. These recent developments are impossible without the continuous advancement seen in the next-generation sequencing platforms; thus, a brief introduction and analysis of the available sequencing platforms are presented here to have a clear picture of the workflow. Concluding the topic is the discussion about different pipelines applied to analyze data produced by sequencing techniques and have a significant role in interpreting the outcome of a particular experiment. A plethora of different software and tools are incorporated in the automated pipelines or individually available to perform manual metagenomic analysis. Here we describe 8-10 advanced, efficient pipelines used for analysis that explain their respective workflows to simplify the whole analysis process.
Host inflammatory responses are key to protection against injury; however, persistent inflammation is detrimental and contributes to morbidity and mortality. Herein, we demonstrated the ...anti-inflammatory role of Arteannuin-B (
) and its new spirocyclic-2-isoxazoline derivative
and their side effects in acute inflammatory condition in vivo using LPS-induced cytokines assay, carrageenan-induced paw edema, acetic acid-induced writhing and tail immersion. The results show that the spirocyclic-2-isoxazoline derivative is a potent anti-inflammatory agent with minimal cell toxicity as compared to Arteannuin-B. In addition, the efficacies of these compounds were also validated by flow cytometric, computational, and histopathological analysis. Our results show that the anti-inflammatory response of
significantly reduces the ability of mouse macrophages to produce NO, TNF-α, and IL-6 following LPS stimulation. Therefore, JR-9 is a prospective candidate for the development of anti-inflammatory drugs and its molecular mechanism is likely related to the regulation of NF-κB and MAPK signaling pathway.
Epilepsy is a chronic neurological disorder affecting 70 million people globally. One of the fascinating attributes of brain microvasculature is the (BBB), which controls a chain of distinct features ...that securely regulate the molecules, ions, and cells movement between the blood and the parenchyma. The barrier's integrity is of paramount importance and essential for maintaining brain homeostasis, as it offers both physical and chemical barriers to counter pathogens and xenobiotics. Dysfunction of various transporters in the (BBB), mainly ATP binding cassette (ABC), is considered to play a vital role in hampering the availability of antiepileptic drugs into the brain. ABC (ATP-binding cassette) transporters constitute a most diverse protein superfamily, which plays an essential part in various biological processes, including cell homeostasis, cell signaling, uptake of nutrients, and drug metabolism. Moreover, it plays a crucial role in neuroprotection by out-flowing various internal and external toxic substances from the interior of a cell, thus decreasing their buildup inside the cell. In humans, forty-eight ABC transporters have been acknowledged and categorized into subfamilies A to G based on their phylogenetic analysis. ABC subfamilies B, C, and G, impart a vital role at the BBB in guarding the brain against the entrance of various xenobiotic and their buildup. The illnesses of the central nervous system have received a lot of attention lately Owing to the existence of the BBB, the penetration effectiveness of most CNS medicines into the brain parenchyma is very limited (BBB). In the development of neurological therapies, BBB crossing for medication delivery to the CNS continues to be a major barrier. Nanomaterials with BBB cross ability have indeed been extensively developed for the treatment of CNS diseases due to their advantageous properties. This review will focus on multiple possible factors like inflammation, oxidative stress, uncontrolled recurrent seizures, and genetic polymorphisms that result in the deregulation of ABC transporters in epilepsy and nanotechnology-enabled delivery across BBB in epilepsy.
Inflammation involves a dynamic network that is highly regulated by signals that initiate the inflammation process as well as signals that downregulate it. However, an imbalance between the two leads ...to tissue damage. Throughout the world, inflammatory disease becomes common in the aging society. The drugs which are used clinically have serious side effects. Natural products or compounds derived from natural products show diversity in structure and play an important role in drug discovery and development.
Oreganum Vulgare is used in traditional medicine for various ailments including respiratory and rheumatic disorders, severe cold, suppression of tumors. The current study aims to evaluate the anti-inflammatory potential by evaluating various in vitro parameters.
Inflammation-induced in macrophages via LPS is the most accepted model for evaluating the antiinflammatory activity of various plant extracts and lead compounds.
The extracts (OVEE, OVEAF) as well as the isolated compound(OVRA)of Oreganum Vulgare inhibit the pro-inflammatory cytokines (IL-6 and TNF-α) and NO without affecting cell viability.
Our study established that the leaf extracts of Oreganum vulgare L. exhibit anti-inflammatory activity and thus confirm its importance in traditional medicine.
Spiroisoxazoline analogues of arteannuin B were synthesized through 1, 3-dipolar cycloaddition of arteannuin B with aryl nitrile oxides and screened for anti-inflammatory activity in RAW 264.7 ...macrophage cells. Among all 8i, 8m and 8n were most potent for IL-6, TNF-α, and LPS induced nitric oxide production in RAW 264.7 cells than the parent compound.
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•Synthesis of spiro-isoxazoline analogues of arteannuin B (1) with aryl nitrile oxides 7.•Compounds 8i, 8m and 8n were most potent of cytokines IL-6 with IC50 1.5, 0.17, 0.56 µM.•Compounds 8i, 8m and 8n potent inhibition of NO with IC50 value 0.3, 0.09, 0.2 µM.
A library of new spiroisoxazoline analogues of arteannuin B was synthesized through 1, 3-dipolar cycloaddition in stereoselective fashion and consequently screened for anti-inflammatory activity in RAW 264.7 macrophage cells. Three potent analogues (8i, 8 m, and 8n) were found to attenuate the LPS induced release of cytokines IL-6 and TNF-α more potently than the parent molecule. Also, the inhibition of LPS induced nitric oxide production in these cells show moderate to high efficacy. None of the three potent molecules have altered the viability of RAW 264.7 cells following 48 h incubation suggesting that the inhibition of cytokines and nitric oxide production exhibited in the cells was not due to toxicity. In addition, these compounds exhibit an IC50 range of 0.17 µM-1.57 µM and 0.09 µM-0.35 µM for the inhibition of IL-6 release and nitric oxide production respectively. The results disclose potent inhibition of pro-inflammatory mediators which are encouraging and warrant further investigations to develop new therapeutic agents for inflammatory diseases.
The graphical abstract representing the role of Bakuchiol on different immunological parameters.
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•Bakuchiol isolated from Psoralea corylifolia a folkloric medicinal plant well known ...for its tremendous medicinal properties.•Anti-inflammatory potential of Bakuchiol was evaluated in in-vitro and in-vivo assays.•Bakuchiol found to be immunosuppressive in various in-vitro and in-vivo assays.•Bakuchiol blocks the phosphorylation of IKKα/β, IκBα and NF-κBp65 thereby exhibiting anti-inflammatory potential.
Bakuchiol (BAK) has been reported to have a diverse pharmacological property as an antibiotic, anti-cancer, anti-hypolipidemic, anti-inflammatory and anti-convulsant agent. This study aimed to elucidate the immunomodulation and anti-inflammatory mechanism of bakuchiol using lipopolysaccharide stimulated RAW 264.7 macrophages and various animal models. The present study has shown that BAK significantly suppressed the pro-inflammatory cytokine expression in a dose-dependent manner and its oral administration significantly decreased delayed hypersensitivity responses as compared to control group. The assessment of immunomodulatory activity was carried out by the testing Hemagglutinating antibody (HA) titer, delayed type hypersensitivity (DTH) responses and phagocytic index by carbon clearance test. On the other hand, it showed significant decrease in circulating antibody titer and carbon clearance assay in a concentration-dependent manner. BAK has significantly potentiated the cellular immunity as well as humoral immunity by facilitating the footpad thickness responses in sheep RBCs in sensitized mice by significantly decreasing circulating antibody titer. Molecular studies revealed that BAK inhibited the activation of upstream mediator nuclear factor-κB by suppressing the phosphorylation of IκBα and p65. The responses were statistically significant as compared with the control (*p < 0.05, **p < 0.01).
