Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin’s anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

In Silico Screening of Potential Phytocompounds from Several Herbs against SARS-CoV-2 Indian Delta Variant B.1.617.2 to Inhibit the Spike Glycoprotein Trimer

In October 2020, the SARS-CoV-2 B.1.617 lineage was discovered in India. It has since become a prominent variant in several Indian regions and 156 countries, including the United States of America. The lineage B.1.617.2 is termed the delta variant, harboring diverse spike mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD), which may heighten its immune evasion potentiality and cause it to be more transmissible than other variants. As a result, it has sparked substantial scientific investigation into the development of effective vaccinations and anti-viral drugs. Several efforts have been made to examine ancient medicinal herbs known for their health benefits and immune-boosting action against SARS-CoV-2, including repurposing existing FDA-approved anti-viral drugs. No efficient anti-viral drugs are available against the SARS-CoV-2 Indian delta variant B.1.617.2. In this study, efforts were made to shed light on the potential of 603 phytocompounds from 22 plant species to inhibit the Indian delta variant B.1.617.2. We also compared these compounds with the standard drug ceftriaxone, which was already suggested as a beneficial drug in COVID-19 treatment; these compounds were compared with other FDA-approved drugs: remdesivir, chloroquine, hydroxy-chloroquine, lopinavir, and ritonavir. From the analysis, the identified phytocompounds acteoside (−7.3 kcal/mol) and verbascoside (−7.1 kcal/mol), from the plants Clerodendrum serratum and Houttuynia cordata, evidenced a strong inhibitory effect against the mutated NTD (MT-NTD). In addition, the phytocompounds kanzonol V (−6.8 kcal/mol), progeldanamycin (−6.4 kcal/mol), and rhodoxanthin (−7.5 kcal/mol), from the plant Houttuynia cordata, manifested significant prohibition against RBD. Nevertheless, the standard drug, ceftriaxone, signals less inhibitory effect against MT-NTD and RBD with binding affinities of −6.3 kcal/mol and −6.5 kcal/mol, respectively. In this study, we also emphasized the pharmacological properties of the plants, which contain the screened phytocompounds. Our research could be used as a lead for future drug design to develop anti-viral drugs, as well as for preening the Siddha formulation to control the Indian delta variant B.1.617.2 and other future SARS-CoV-2 variants.

Establishment and Characterization of NCC-MFS5-C1: A Novel Patient-Derived Cell Line of Myxofibrosarcoma

Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using a large number of tumor cell lines has been attempted to discover novel therapeutic candidate drugs for common cancers. However, the number of MFS cell lines is extremely small because of its low incidence—this hinders the conduction of screening studies and slows down the development of therapeutic drugs. To overcome this problem, we established a novel MFS cell line, NCC-MFS5-C1, which was shown to harbor typical MFS genetic abnormalities and thus had useful properties for in vitro studies. We conducted the largest integrated screening analysis of 210 drugs using NCC-MFS5-C1 cells along with four MFS cell lines, which we previously reported. Bortezomib (a proteasome inhibitor) and romidepsin (a histone deacetylase inhibitor) showed stronger antitumor effects than the standard drug, doxorubicin. Therefore, the NCC-MFS5-C1 cell line can potentially contribute to elucidating MFS pathogenesis and developing a novel MFS treatment.

Identification of ∆9-tetrahydrocannabinol (THC) impairment using functional brain imaging

The primary cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC), causes intoxication and impaired function, with implications for traffic, workplace, and other situational safety risks. There are currently no evidence-based methods to detect cannabis-impaired driving, and current field sobriety tests with gold-standard, drug recognition evaluations are resource-intensive and may be prone to bias. This study evaluated the capability of a simple, portable imaging method to accurately detect individuals with THC impairment. In this double-blind, randomized, cross-over study, 169 cannabis users, aged 18–55 years, underwent functional near-infrared spectroscopy (fNIRS) before and after receiving oral THC and placebo, at study visits one week apart. Impairment was defined by convergent classification by consensus clinical ratings and an algorithm based on post-dose tachycardia and self-rated “high.” Our primary outcome, PFC oxygenated hemoglobin concentration (HbO), was increased after THC only in participants operationalized as impaired, independent of THC dose. ML models using fNIRS time course features and connectivity matrices identified impairment with 76.4% accuracy, 69.8% positive predictive value (PPV), and 10% false-positive rate using convergent classification as ground truth, which exceeded Drug Recognition Evaluator-conducted expanded field sobriety examination (67.8% accuracy, 35.4% PPV, and 35.4% false-positive rate). These findings demonstrate that PFC response activation patterns and connectivity produce a neural signature of impairment, and that PFC signal, measured with fNIRS, can be used as a sole input to ML models to objectively determine impairment from THC intoxication at the individual level. Future work is warranted to determine the specificity of this classifier to acute THC impairment.ClinicalTrials.gov Identifier: NCT03655717

COMPARISON OF HEPATOPROTECTIVE ACTIVITY OF NISHA LAUHA (NL) AND NISHA LAUHA WITHOUT LAUHA BHASMA (NLWL) AGAINST CCL4 INDUCED HEPATOTOXICITY IN WISTAR RATS

Introduction: Many herbal drugs are used to treat liver diseases, but the dose of the herbal drug is high, and they have lesser palatability. An ideal medicine is a medicine that is effective, easy palatable and produces quick action in a low dose. It is possible by adding metals like Lauha (Iron) to the herbal drugs. Objective: To compare the hepatoprotective effect of Nisha Lauha (NL) and Nisha Lauha without Lauha Bhasma (NLWL) in experimental rats. Materials and methods: 40 rats were taken divided into five groups, and each group contained eight rats. Among these groups, four groups receive 0.2 ml of injection containing the 0.1 ml CCL4 plus 0.1 ml liquid paraffin given intraperitoneally for 28 days to induce Hepatotoxicity. Both Test groups received NL and NLWL at a dose of 45mg/kg bd. wt. and 450mg/kg bd. wt. respectively for 28 days. The standard group receives silymarin at a 100 mg/kg bd dose. wt. for 28 days by oral route. The hepatoprotective effect was analyzed using biochemical parameters and histopathological study of the liver. Results: Both the Test and standard groups do not show toxic effects against CCL4 induced hepatotoxicity and lower the dose of the herbal drug due to the addition of Lauha. Conclusion: The result suggests that both test group NL and NL without Lauha Bhasma shows the hepatoprotective activity as equivalent to standard drug silymarin. The addition of Lauha Bhasma to herbal drugs decreases the dose without affecting the drug’s efficacy against the hepatoprotective effect.

Reverse dot blot hybridization assay— An expeditious diagnostic tool for drug resistant TB

Tuberculosis (TB) is one of the leading infectious diseases that is highly transmissible. It is reported to cause approximately 10 million infections and 1.4 million deaths globally in the year of 2019.¹ Prompt detection and treatment of TB are essential to intercept the proliferation of the disease. In the case of drug- resistant TB, failure to detect the resistance of anti TB drugs may give rise to extensively drug- resistant tuberculosis (XDR-TB). Thus, the rapid detection of drug resistance is vital;, however, the current standard drug susceptibility tests (DST) may take up to 12 weeks raising an alarming concern.² A study was done in China by Li Wan et al, on the accuracy of the reverse dot blot hybridization assay (RDBH) for rapidly detecting the resistance of four anti TB drugs (rifampicin (RIF), isoniazid (INH), streptomycin (SM) and ethambutol (EMB)) in mycobacterium tuberculosis (MTB) isolates.³ Continuous...

Assessment of Anthelmintic Property and Insilico study of phytocompounds in roots of Dechaschistia crotonifolia Wight & Arn.

Background:Worm infections in developing countries were reported high. Phytoconstituents have been a vital role for the treatment of many ailments. The current study was aimed assess for anthelmintic activity of different root extracts of Dechaschistia crotonifolia Wight & Arn. belongs to the family Ebanaceae against Pheretima posthuma. Further Insilico study was carried out for phytocompounds present in Dechaschistia. Results: The chloroform, ethylacetate and ethanol extract of Dechaschistia crotonifolia Wight & Arn. were considered for the study of anthelmintic property on earthworms at concentrations 20 mg/ml, 40 mg/ml and 60 mg/ml. During this study, the parameters paralysis time (Pt) and Death Time (Dt) of adult Indian earthworms was observed. As a standard and control Albendazole 10 mg/ml and 2% Tween 80 in distilled water were taken respectively. The study resulted that ethanolic extract was significant when compared with the Albendazole 10 mg/ml. Docking studies revealed the all phytocompounds in Dechaschistia shown binding affinity, however comparatively scopoletin and stigmasterol had shown a good binding affinitiy about -7.7 Kcal/mol and -7.6 Kcal/mol compared to standard drug Albendazole which was shown about -8.7 Kcal/mol. Conclusion: The study revealed that the ethanol extract of Dechaschistia crotonifolia Wight & Arn. at a concentration of 60mg/ml exhibited a stronger anthelmintic property compared to Albendazole 10mg/ml. A dose dependent anthelmintic activity is exerted by all the extracts in an ascending manner Chloroform<Ethyl acetate<Ethanol. These observations were made evidenced by docking studies of phytocompounds in Dechaschistia as the phytocompounds were shown excellent docking score when compared with standard Albendazole.

Synthesis and biological evaluation of pyrazole analogues linked with 1,2,3-triazole and 4-thiazolidinone as antimicrobial agents

A new series of 2-[3-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-4-pyrazolyl]-3-aryl-1,3-thiazolan-4-one 5(a-i) have been designed, synthesized and evaluated for their in vitro antibacterial activity against Gram positive bacteria viz. Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538p), Micrococcus luteus (IFC 12708) and Gram negative bacteria viz. Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), Escherichia coli (ATCC 25922) the antifungal activity against Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), Trichophyton mentagrophytes (IFO 40996). Antibacterial evaluation indicates that compounds containing 4-methoxyphenyl 5c, 4-fluorophenyl 5d and 2,5-difluorophenyl 5h groups on thiazolidinone ring showed significant activity equal to that of standard drug. The antifungal evaluation shows that compound 5c is highly active against A. fumigatus, compound 5d and 5h were also active against C. albicans and A. fumigatus.

Preliminary Phytochemical Analysis: In-Vitro Comparative Evaluation of Anti-arthritic and Anti-inflammatory Potential of Some Traditionally Used Medicinal Plants

Background: Colchicum autumnale, Strychnous nux-vomica and Aloe barbadensis are the medicinal plants clinically utilized for the management of rhuematic disorders. Purpose: The present work was focused to evaluate the in-vitro anti-arthritic and anti-inflammatory activities of Colchicum ( Colchicum autumnale), Nux-vomica ( Strychnous nux-vomica), and Aloe-vera ( Aloe barbadensis). Research Design: Primarily, the aqueous-ethanolic extracts of these medicinal plants were phytochemically screened followed by Fourier Transform Infrared (FTIR) analysis. Anti-arthritic activity by protein denaturation method and anti-inflammatory activity by human red blood cell (HRBC) membrane stabilization method at the concentration of 125, 250, and 500 µg/mL along with standard were performed. Results: Phytochemical screening revealed that alkaloids, saponins, terpenoids, phenols, and anthraquinones were found in all the extracts, and organic acids, amine group, aromatic or aliphatic compounds, esters and halogens, and phenolics were identified by FTIR. Protein denaturation method revealed that colchicum, nux-vomica, and aloe-vera showed maximum 98.5%, 99.6%, and 72.3% of inhibition at 500 µg/mL compared with that of standard drug, that is, Diclofenac sodium. Membrane stabilization method showed that colchicum, nux-vomica, and aloe-vera showed maximum 40.20%, 35.67%, and 40.1% protection at 500 µg/mL when compared with standard drug. Conclusion: It is concluded from the current study that extracts of colchicum, nux-vomica, and aloe-vera showed more potent effect and thus can be used as alternative options for the management of inflammatory and arthritic ailments.