Coronavirus disease (COVID-19) has killed millions of people since first reported in Wuhan, China, in December 2019. Intriguingly, Withania somnifera (WS) has shown promising antiviral effects against numerous viral infections, including SARS-CoV and SARS-CoV-2, which are contributed by its phytochemicals. This review focused on the updated testing of therapeutic efficacy and associated molecular mechanisms of WS extracts and their phytochemicals against SARS-CoV-2 infection in preclinical and clinical studies with the aim to develop a long-term solution against COVID-19. It also deciphered the current use of the in silico molecular docking approach in developing potential inhibitors from WS targeting SARS-CoV-2 and host cell receptors that may aid the development of targeted therapy against SARS-CoV-2 ranging from prior to viral entry until acute respiratory distress syndrome (ARDS). This review also discussed nanoformulations or nanocarriers in achieving effective WS delivery to enhance its bioavailability and therapeutic efficacy, consequently preventing the emergence of drug resistance, and eventually therapeutic failure.

Background : Obesity has become a global issue, leading to increased risk of metabolic syndrome, which encompasses diabetes, cardiovascular disease, stroke, hypertension, and certain cancers. However, obesity is difficult to control through diet and exercise alone, as they are difficult to implement. Objective: The objective of this review is to elucidate the active constituents that can be obtained from various natural sources that act as anti-obesity agents. Due to the global rise in the prevalence of obesity, an urgent need to prevent and control it has arisen. Methods: For this review, we compiled information about natural anti-obesity products through an electronic search of the articles available via PubMed, Scopus, and other internet sources for the period 1975-2019 and included our own research. We analyzed and organized data on various natural products in popular use in addition to relevant pharmacognostic and biological studies. The products’ mechanisms of action were also investigated. Conclusion: Consumption of diets that include high amounts of active anti-obesity natural compounds is a promising strategy for the suppression of lipid accumulation and adipogenesis in obese individuals.

Background: Thyroid hormones play a vital role in regulating our body’s metabolism. Two important thyroid hormones released from the thyroid gland are tri-iodothyronine (T3) and tetra-iodothyronine (T4). Thyroid-stimulating hormone and thyroid regulating hormone control the T3 and T4 levels in our body. Increased TSH levels indicate hypothyroidism and decreased TSH levels indicate hyperthyroidism. Iodine is a crucial nutrient for the synthesis of thyroid hormones and is mostly obtained from our diet. Other essential nutrients for the thyroid hormones formation include selenium, iron, vitamin D, vitamin B12, etc. Dietary changes in these nutrients can result in alterations in thyroid function and structure. Although normally, the hormonal diseases cannot be cured, but we can improve their signs and symptoms using suitable dietary supplements. Objective: The aim of the study was to thoroughly analyze the various benefits and risks associated with the use of dietary supplements for the prevention and treatment of various thyroid disorders, like hypothyroidism, as seen in Hashimoto’s thyroiditis; hyperthyroidism, as seen in Graves’ disease; sick euthyroidism and subclinical hypothyroidism. Methods: Literature was searched using the search terms “dietary supplements+thyroid diseases” on Pubmed, Google Scholar, Scopus, Cochrane Library, and other search engines, and data were collected from 1967 to November, 2021, including research inputs from the authors. The literature was thoroughly searched, and deep knowledge was acquired on this topic, which was then sequentially organized and summarized using suitable tables and figures. Conclusion: After analyzing various studies on this topic, we arrived at the conclusion that although there are various claimed and observed health benefits of dietary supplements in the prevention and treatment of various thyroid disorders, still several studies have shown too many risks to be associated with the use of dietary supplements, and people using these products should be aware of these risks in order to use them very judiciously for the improvement of their thyroid status.

BACKGROUND: In this study, we define the mechanistic association between long noncoding RNA: ENST00000495536 (lnc-536) and transcription factor HOXB13 (homeobox B13) in mediating proproliferative smooth muscle phenotype associated with pulmonary hypertension. METHODS: In vitro knockdown or knockin, along with RNA pull-down and immunoprecipitation studies, were used to evaluate the role of lnc-536 and HOXB13 in regulating pulmonary arterial smooth muscle cell (PASMCs) phenotype. The in vivo role was determined by injecting lnc-536 antisense oligos in pulmonary hypertensive rats. RESULTS: Increased levels of lnc-536 promote the proliferative phenotype of PASMCs by downregulating the expression of the tumor suppressor: HOXB13. Knockdown of lnc-536 and overexpression of HOXB13 in proliferative PASMCs resulted in increased expression of VGLL4 (vestigial-like family member 4), a negative regulator of Hippo and Wnt (Wingless-related integration site) signaling pathways, with a corresponding decrease in TEAD4 (TEA domain family member 1) expression. The lnc-536 pull-down assay and RNA-immunoprecipitation demonstrated the interactions of lnc-536 with RBP (RNA-binding protein): RBM25 (RNA-binding motif 25) and direct interactions of RBM25 with SFPQ (splicing factor proline/glutamine-rich), a transcriptional regulator that has a binding motif on HOXB13. The knockdown of RBM25 in the hyperproliferative PASMCs resulted in increased interactions of SFPQ and HOXB13 mRNA while attenuating PASMC proliferation. Furthermore, the increased levels of lnc-536 and decreased levels of HOXB13 were observed in PASMCs from idiopathic pulmonary hypertension patients but not in cells from familial pulmonary hypertension patients. We confirmed that lnc-536 contributes to the RBM25-mediated remodeling of the SFPQ-HOXB13 complex in the idiopathic PAH-PASMCs as well. Finally, in vivo inhibition of lnc-536 using GapmeRs (Gapmer antisense oligonucleotides) in Sugen-hypoxia and HIV-transgenic pulmonary hypertension rats prevented the increase in right ventricular systolic pressure, right ventricular hypertrophy/fibrosis, and pulmonary vascular remodeling with a parallel increase in HOXB13 expression in rat PASMCs. CONCLUSIONS: Lnc-536 acts as a decoy for RBM25, which in turn sequesters SFPQ, leading to a decrease in HOXB13 expression and hyperproliferation of smooth muscle cells by potentially regulating Wnt and Hippo signaling associated with PAH development.

Background: Momordica charantia Linnaeus (Cucurbitaceae family), known as bitter melon is an annual climbing vine, which grows in tropical regions and its fruits are consumed as a vegetable in Asian countries. Traditionally various parts of the plant such as fruits, seeds, leaves, flowers, etc. have been used for medicinal purposes. Its fruit is used as an anti-diabetic, laxative, anthelmintic, emetic, and anti-obesity, for respiratory problems, ulcers, wounds, rheumatism, gout, toothache, and skin diseases. Objective: To perform pharmacognostical evaluation, qualitative and quantitative phytochemical screening, safety and toxicity studies, and in vitro anti-obesity activity evaluation on bitter gourd fruits from Haryana (India). Methods: Organoleptic studies were performed with the naked eye and microscopical studies were performed using the EVOS microscope; physicochemical evaluation, microbial, and mycotoxin studies were performed by adopting the standard procedures detailed in the WHO guidelines (2011); phytochemical screening was performed by following the standard procedures; pesticide residue determination was performed by using GCMS; and in vitro anti-obesity evaluation consisting of in vitro pancreatic lipase, α-amylase, and α-glucosidase evaluation was performed by following the standard procedures. Results: The pharmacognostical standards i.e. macroscopy, microscopy, and physicochemical analyses of the fruits were established and their qualitative and quantitative phytochemical contents revealed the presence of alkaloids, glycosides, flavonoids, tannins, proteins, and amino acids, carbohydrates, fats, and fixed oils, sterols, and triterpenoids, etc. The fruit was found to be free from mycotoxin, microbial contamination, and harmful pesticide residues. The major pesticides found to be present in fruit extract were alpha-BHC, Aldrin, 4, 4’-DDE, Endrin, and4, 4'- DDD and they were present within permissible limits. The total phenolic content in the fruits was found to be 3.49 ± 1.3mg/g gallic acid equivalent/100g. The content of total flavonoids have been expressed as quercetin, catechin, and rutin equivalents, i.e., 1.88 ± 0.16, 122.7 ± 13.8 and 1.978 ± 0.006 mg/g dry weight of fruits respectively and they were present within permissible limits. The α-glucosidase inhibition potential of the alcoholic extract was good with an IC50 value of 173.50 ± 0.33 μg/ml, followed by aqueous extract i.e. 351.00 ± 0.56, whereas the chloroform extract showed milder inhibition with IC50 value of 448.60 ± 0.98 μg/ml. The lipase inhibition potential of aqueous extracts was good with an IC50 value of 140.31 ± 0.48μg/ml, followed by alcoholic extracts, with inhibition of 100.10 μg/ml, whereas the chloroform extracts show lesser inhibition, i.e., 499.83 μg/ml only. Whereas the alcoholic extract shows good α-amylase enzyme inhibition with IC50 value of 425.44 ± 0.63 μg/ml, followed by aqueous extract i.e., 486.12 ± 0.77 μg/ml, and chloroform extract shows lesser activity, i.e., 65. 82 ± 0.41 μg/ml. Conclusion: Identification and authentication of the fruits was performed with the help of pharmacognostical and physicochemical standards, and they could be useful for the monograph preparation of the plant and in controlling the commercial adulteration of the bitter gourd fruits. Safety and toxicity studies have determined that the fruits were fit for consumption. In vitro anti-obesity evaluation findings can be further explored in vivo for testing their therapeutic efficacy in lab animals. Proper identification of the crude drug helps the researchers in reproducing the results and carrying the research forward without wasting time that usually occurs due to misidentification of the crude drug which makes lab results difficult to reproduce.