Promising role of Vitamin D and plant metabolites against COVID-19: Clinical trials review.

Vitamin D possesses immunomodulatory qualities and is protective against respiratory infections. Additionally, it strengthens adaptive and cellular immunity and boosts the expression of genes involved in oxidation. Experts suggested taking vitamin D supplements to avoid and treat viral infection and also COVID-19, on the other hand, since the beginning of time, the use of plants as medicines have been vital to human wellbeing. The WHO estimates that 80 % of people worldwide use plants or herbs for therapeutic purposes. Secondary metabolites from medicinal plants are thought to be useful in lowering infections from pathogenic microorganisms due to their ability to inhibit viral protein and enzyme activity by binding with them. As a result, this manuscript seeks to describe the role of vitamin D and probable plant metabolites that have antiviral activities and may be complementary to the alternative strategy against COVID-19 in a single manuscript through reviewing various case studies.

Prevention of pain on injection of propofol using ice gel pack versus pre-treatment with lignocaine: a randomized controlled trial.

PURPOSE: Regardless of the positive attributes of propofol, it is frequently associated with pain on injection. We compared the efficacy of topical cold thermotherapy using an ice gel pack with intravenous lignocaine pre-treatment for reducing pain on propofol injection. METHODS: This single-blinded randomized controlled trial was conducted in 200 American Society of Anesthesiologists physical status I, II, and III patients scheduled for elective/emergency surgery under general anesthesia. The patients were randomized into two groups: the Thermotherapy group- receiving an ice gel pack proximal to the intravenous cannula for 1 min, or the Lignocaine group-receiving 0.5 mg/kg of lignocaine administered intravenously, with occlusion proximal to the site of the intravenous cannula for 30 s. The primary objective was to compare the overall incidence of pain after propofol injection. The secondary objectives included the incidence of discomfort on the application of an ice gel pack, comparison of dose of propofol needed for induction, and hemodynamic changes at induction, between the two groups. RESULTS: Fourteen patients in the lignocaine group and 15 patients in the thermotherapy group reported pain. The incidence of pain and the distribution of pain scores were comparable among groups (p = 1.00). Patients of the lignocaine group required significantly less amount of propofol for induction as compared to the thermotherapy group (p = 0.001). CONCLUSION: Topical thermotherapy using an ice gel pack was not found superior to lignocaine pre-treatment in alleviating pain on injection of propofol injection. However, topical cold therapy using an ice pack remains a non-pharmacological technique that is easily available, reproducible, and cost-effective. Further studies are required to prove its equivalence to lignocaine pre-treatment. TRIAL REGISTRATION: CTRI (CTRI/2021/04/032950).

Increasing postpartum IUCD coverage through a QI initiative: a step towards reducing the unmet need of postpartum contraception.

BACKGROUND: Unintended pregnancies have a negative impact on the health and economy of a nation, which can be prevented by effective family planning (FP) services. Postpartum intrauterine device (PPIUCD) is a safe and effective FP method which allows women to obtain long-acting contraception before discharge from the point of delivery. We observed poor coverage of deliveries with PPIUCD at our facility. This was the trigger to initiate a quality improvement (QI) initiative to increase the PPIUCD coverage from current rate of 4.5%-10% in 3-month period. METHOD: A fishbone analysis of the problem was done and the following causes were identified: lack of focused counselling for FP, lack of sensitisation and training of resident doctors and inconsistent supply of intrauterine contraceptive devices (IUCDs). A QI team was constituted with representatives from faculty members, residents, interns, nursing officers and FP counsellors. The point of care quality improvement methodology was used. INTERVENTIONS: Daily counselling of antenatal women was started by the counsellors and interns in antenatal wards. A WhatsApp group of residents was made initially to sensitise them; and later for parking of problems and trouble shooting. The residents were provided hands-on training at skills lab. Uninterrupted supply of IUCDs was ensured by provision of buffer stock of IUCDs with respective store keepers. RESULT: The PPIUCD insertion rates improved from 4.5% to 19.2% at 3 months and have been sustained to a current 30%-35% after 1 ½ years of initiation of the project tiding through the turbulence during the COVID-19 pandemic using QI techniques. CONCLUSION: Sensitisation and training of residents as well as creation of awareness among antenatal women through targeted counselling helped improve PPIUCD coverage at the facility. QI initiatives have the potential to facilitate effective implementation of the FP programmes by strategic utilisation of the resources.

Screening of Furanone in Cucurbita melo and Evaluation of its Bioactive Potential Using In Silico Studies.

The work presented here attempts to screen for the presence of 4-Hydroxy-2,5-dimethyl-3(2H)-furanone in fruits and also any bioactive potential present in the fruit extracts. Curcurbita melo was selected for the study, and the fruit was crushed, filtered and extracted with ethyl acetate as the solvent. The resulting extract was subjected to disk diffusion test using Kirby Bauer method for checking its antimicrobial potential. Melon extract showed promising results against different clinical pathogens, 19-mm zone being the largest against Klebsiella pneumoniae and 17 mm against Shigella dysenteriae. GC-MS data of the melon extract confirmed the existence of furanone derivative in the extract. To evaluate the antimicrobial activity, in silico studies were performed using AutoDock 4.0 software, and topoisomerase was used as the target protein molecule for the isolated compound and 3-methyl-2-(2-oxopropyl)furan as the ligand. Further, the results were interpreted using PyMol and Ligplot plus softwares. The results confirmed the presence of molecular interactions between the protein molecule and the ligand. It can be envisaged that these interactions are responsible for the inhibitory effects of the extract .

Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice.

The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3ß- and 17ß-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction.

Identification of Novel Inhibitors of Mycobacterium tuberculosis PknG Using Pharmacophore Based Virtual Screening, Docking, Molecular Dynamics Simulation, and Their Biological Evaluation.

PknG is a Ser/thr protein kinase that plays a crucial role in regulatory processes within the mycobacterial cell and signaling cascade of the infected host cell. The essentiality of PknG in mycobacterial virulence by blocking phagosome-lysosome fusion as well as its role in intrinsic antibiotic resistance makes it an attractive drug target. However, only very few compounds have been reported as Mycobacterium tuberculosis PknG (MtPknG) inhibitors so far. Therefore, in an effort to find potential inhibitors against MtPknG, we report here a sequential pharmacophore-based virtual screening workflow, 3-fold docking with different search algorithms, and molecular dynamic simulations for better insight into the predicted binding mode of identified hits. After detailed analysis of the results, six ligands were selected for in vitro analysis. Three of these molecules showed significant inhibitory activity against MtPknG. In addition, inhibitory studies of mycobacterial growth in infected THP-1 macrophages demonstrated considerable growth inhibition of M. bovis BCG induced through compound NRB04248 without any cytotoxic effect against host macrophages. Our results suggest that the compound NRB04248 can be explored for further design and optimization of MtPknG inhibitors.

Pharmacognostical evaluation of Cardiospermum halicacabum Linn. leaf and stem.

BACKGROUND: Cardiospermum halicacabum Linn (Sapindaceae) is an important medicinal plant in the traditional system of medicine, known as karnasphota. The root of it is officially included in Ayurvedic Pharmacopoeia for its therapeutic uses such as jvara, kustha, pandu, ksaya and sandhivata etc. As no detailed analysis of macroscopy, microscopy characters of the plant, except root, have been carried out till date, it was thought worth to carry out the detailed macroscopic and microscopic study of leaves and stem, following standard pharmacognostical procedures. MATERIALS AND METHODS: Pharmacognostic studies of C. halicacabum were carried out, and in this, the macroscopic, microscopic, physicochemical, fluorescence and phytochemical analyses were done. Physicochemical parameters such as total ash, moisture content, extractive values were determined by World Health Organization guidelines. The microscopic features of leaf and stem components were observed. RESULTS: Macroscopically the leaves are bi-ternate, ovate-lanceolate in shape with dentate margin. Microscopically, leaf shows prominent midrib and thin dorsiventral lamina. The midrib shows the presence of epidermal layers, angular collenchyma, palisade cells and vascular strands comprised of thin walled xylem and thick walled phloem elements. The lamina shows prominent, narrow and cylindrical upper epidermis. The upper epidermal cells are large and contain mucilage, whereas lower epidermis possesses thin, small and elliptical epidermal cells. The mesophyll was differentiated into two zones upper and lower. The upper zones show narrow cylindrical palisade cells and lower zone shows 2-3 layers of loosely arranged spongy parenchyma cells. In the Paradermal section of the lamina we observe anomocytic stomata. The transverse section of stem shows a pentagonal appearance with five short blunt ridges and prominent cuticle. Parenchymatous cells, cortical sclerenchyma, lignified xylem fibers, phloem and pit were also found. In the powder microscopy of whole plant, glandular trichomes, non-glandular trichomes, fragments of lamina, xylem elements, parenchyma cells and fibers are observed. Phytochemical screening reveals that the C. halicacabum extract contains glycosides, carbohydrates, flavonoids, phytosterols, phenolic compounds and saponin. CONCLUSION: Various pharmacognostic characters observed in this study help in identification, quality, purity and standardization of C. halicacabum.

[6]-Gingerol induces bone loss in ovary intact adult mice and augments osteoclast function via the transient receptor potential vanilloid 1 channel.

SCOPE: [6]-Gingerol, a major constituent of ginger, is considered to have several health beneficial effects. The effect of 6-gingerol on bone cells and skeleton of mice was investigated. METHODS AND RESULTS: The effects of 6-gingerol on mouse bone marrow macrophages and osteoblasts were studied. 6-Gingerol-stimulated osteoclast differentiation of bone marrow macrophages but had no effect on osteoblasts. Capsazepine, an inhibitor of TRPV1 (transient receptor potential vanilloid 1) channel, attenuated the pro-osteoclastogenic effect of 6-gingerol or capsaicin (an agonist of TRPV1). Similar to capsaicin, 6-gingerol stimulated Ca(2) + influx in osteoclasts. The effect of daily feeding of 6-gingerol for 5 wk on the skeleton of adult female Balb/cByJ mice was investigated. Mice treated with capsaicin and ovariectomized (OVx) mice served as controls for osteopenia. 6-Gingerol caused increase in trabecular osteoclast number, microarchitectural erosion at all trabecular sites and loss of vertebral stiffness, and these effects were comparable to capsaicin or OVx group. Osteoclast-specific serum and gene markers of 6-gingerol-treated mice were higher than the OVx group. Bone formation was unaffected by 6-gingerol. CONCLUSION: Daily feeding of 6-gingerol to skeletally mature female mice caused trabecular osteopenia, and the mechanism appeared to be activation of osteoclast formation via the TRPV1 channel.

Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice.

Medicarpin, a pterocarpan class of naturally occurring benzopyran furanobenzene compound was synthesized in gram scale to investigate its effects on murine bone cells and in ovariectomized (OVx) mice. Medicarpin, at as low as 10(-10)M suppressed osteoclastogenesis in bone marrow cells (BMCs). Medicarpin-induced apoptosis of mature osteoclasts isolated from long bones. Effects of medicarpin in osteoclasts appear to be independent of estrogen receptor (ER) activation as ICI 180,782 failed to abrogate its effects on osteoclasts. In calvarial osteoblasts, medicarpin (10(-10)M) blocked nuclear factor kappaB (NF-kappaB) signaling assessed by tumor necrosis factor alpha (TNFalpha)-stimulated nuclear translocation of p65 subunit of NF-kappaB. Medicarpin also inhibited the expression of TNFalpha in mouse calvarial osteoblasts. This effect was ER dependent as ICI 180,782 reversed the suppressive effect of medicarpin on TNFalpha mRNA levels in osteoblasts. In addition, like 17beta-estradiol, presence of medicarpin inhibited TNFalpha-induced upregulation of interleukin-1, and -6 mRNA levels in osteoblasts. In co-cultures consisting of calvarial osteoblasts and BMCs, presence of medicarpin increased osteoprotegerin (OPG)/receptor activator of NF-kappaB ligand (RANKL) ratio and reduced mRNA levels of osteoclast markers including tartrate-resistant acid phosphatase and RANK. OVx mice administered medicarpin (10.0mgkg(-1)day(-1)) orally for 30days had reduced formation of osteoclasts but increased formation of osteoprogenitor cells in BMCs compared with OVx+vehicle group. Medicarpin treatment to OVx mice maintained parameters of trabecular microarchitecure. Medicarpin exhibited no uterine estrogenicity. Our findings point towards direct and indirect inhibitory effects of medicarpin on osteoclastogenesis in vitro that contribute to its bone sparing effect in OVx mice.