Indigenous wisdom of a Kwatha to treat NASH: An insight into the mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most common severe liver disease globally, progressing further into nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Vasaguduchyadi Kwatha (VK) is an Ayurvedic formulation traditionally used to treat liver diseases and other metabolic complications. This study is an ethnopharmacological approach to unravel this indigenous remedy. AIM OF THE STUDY: We aimed to discover the probable mechanism of action of VK against NASH in this study, using network pharmacology, molecular docking, in vitro study, and preclinical investigation. METHODS AND RESULTS: Among the 55 components identified, 10 were confirmed based on mass, elution charecteristics, MS/MS analysis data, and fragmentation rules. Computational study indicated 92 targets involved in the central pathways of NASH, out of which only 15 targets and 9 VK constituents have significant docking scores. In vitro and in vivo analysis results showed that VK significantly reduces weight gain and improves insulin sensitivity, dyslipidemia, steatohepatitis and overall histological features of NASH compared to saroglitazar (SGZR). CONCLUSION: Our detailed study yielded three signalling pathways related to NASH on which VK has maximum effect, bringing up a probable alternative treatment for NASH.

Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases.

Neurological disorders incidences are increasing drastically due to complex pathophysiology, and the nonavailability of disease-modifying agents. Several attempts have been made to identify new potential chemicals to combat these neurological abnormalities. At present, complete abolishment of neurological diseases is not attainable except for symptomatic relief. However, dietary recommendations to help brain development or improvement have increased over the years. In recent times, cruciferous vegetables and their phytochemicals have been identified from preclinical and clinical investigations as potential neuroprotective agents. The present review highlights the beneficial effects and molecular mechanisms of phytochemicals such as indole-3-carbinol, diindolylmethane, sulforaphane, kaempferol, selenium, lutein, zeaxanthin, and vitamins of cruciferous vegetables against neurological diseases including Parkinson's disease, Alzheimer's disease, stroke, Huntington's disease, autism spectra disorders, anxiety, depression, and pain. Most of these cruciferous phytochemicals protect the brain by eliciting antioxidant, anti-inflammatory, and antiapoptotic properties. Regular dietary intake of cruciferous vegetables may benefit the prevention and treatment of neurological diseases. The present review suggests that there is a lacuna in identifying the clinical efficacy of these phytochemicals. Therefore, high-quality future studies should firmly establish the efficacy of the above-mentioned cruciferous phytochemicals in clinical settings.

Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have shown that hydroxychloroquine (HCQ) significantly inhibits SARS-CoV-2 infections in vitro. OBJECTIVE: Since the phytoconstituents of Cinchona officinalis (CO) are similar to those of HCQ, the objective of this study was to test the antiviral potential of different homeopathic formulations of CO. METHODS: An analysis of the molecular composition of CO was carried out using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by a detailed docking study. The constituents of CO were docked against various targets of SARS-CoV-2, and the binding potential of the phytoconstituents was compared and quantified. The ligand with the lowest Glide docking score is considered to have the best binding affinity. The cytotoxicity of several homeopathic formulations, including CO mother tincture (CO-MT), was also checked on VeroE6 cells. A known antiviral, remdesivir, was used as a positive control for the in vitro assays to evaluate the effects of CO-MT against SARS-CoV-2-infected VeroE6 cells. RESULTS: Molecular docking studies showed that constituents of CO exhibited binding potential to various targets of SARS-CoV-2, including Mpro, PLpro, RdRp, nucleocapsid protein, ACE2 (in host) and spike protein. Quinoline, one of the constituents of CO, can potentially bind the spike protein of SARS-CoV-2. Quinic acid showed better binding capabilities with Mpro, PLpro RdRp, nucleocapsid protein and ACE2 (allosteric site) than other constituents. Quinidine exhibited better binding to ACE2. Compared to HCQ, other phytoconstituents of CO had the equivalent potential to bind the RNA-dependent RNA polymerase, nucleocapsid protein, Mpro, PLpro and spike protein of SARS-CoV-2. In vitro assays showed that homeopathic CO-MT was not cytotoxic and that CO-MT and remdesivir respectively caused 89% and 99% inhibition of SARS-CoV-2 infection in VeroE6 cells. CONCLUSION: Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in COVID-19.

Keratinocytes: An Enigmatic Factor in Atopic Dermatitis.

Atopic dermatitis (AD), characterized by rashes, itching, and pruritus, is a chronic inflammatory condition of the skin with a marked infiltration of inflammatory cells into the lesion. It usually commences in early childhood and coexists with other atopic diseases such as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc. With a prevalence rate of 1-20% in adults and children worldwide, AD is gradually becoming a major health concern. Immunological aspects have been frequently focused on in the pathogenesis of AD, including the role of the epidermal barrier and the consequent abnormal cytokine expressions. Disrupted epidermal barriers, as well as allergic triggers (food allergy), contact allergens, irritants, microbes, aggravating factors, and ultraviolet light directly initiate the inflammatory response by inducing epidermal keratinocytes, resulting in the abnormal release of various pro-inflammatory mediators, inflammatory cytokines, and chemokines from keratinocytes. In addition, abnormal proteinases, gene mutations, or single nucleotide polymorphisms (SNP) affecting the function of the epidermal barrier can also contribute towards disease pathophysiology. Apart from this, imbalances in cholinergic or adrenergic responses in the epidermis or the role played by immune cells in the epidermis such as Langerhans cells or antigen-presenting cells can also aggravate pathophysiology. The dearth of specific biomarkers for proper diagnosis and the lack of a permanent cure for AD necessitate investigation in this area. In this context, the widespread role played by keratinocytes in the pathogenesis of AD will be reviewed in this article to facilitate the opening up of new avenues of treatment for AD.