Cordyceps inhibits ceramide biosynthesis and improves insulin resistance and hepatic steatosis.

Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps. Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila. Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.

Therapeutic Potentials of Syzygium fruticosum Fruit (Seed) Reflected into an Array of Pharmacological Assays and Prospective Receptors-Mediated Pathways.

Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed's fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleep during the open field and thiopental-induced sleeping tests, respectively. In parallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed acetic acid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatory activity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC-MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski's rule and safety confirmation showed strong binding affinity (molecular docking) against the receptors of each model used. To conclude, the S. fruticosum seed is a prospective source of health-promoting effects that can be an excellent candidate for preventing degenerative diseases.

Drug Repurposing Approach against Novel Coronavirus Disease (COVID-19) through Virtual Screening Targeting SARS-CoV-2 Main Protease.

Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 Mpro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex's conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex's firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (Mpro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug's activity.

An integrated exploration of pharmacological potencies of Bischofia javanica (Blume) leaves through experimental and computational modeling.

Bischofia javanica (Blume), an edible wild plant, has both prospective nutraceutical and therapeutic properties. Here, we intended to explore the pharmacological potentials of the methanol extract of B. javanica (MEBJ) through integrated approaches. Phytochemical screening revealed the presence of important phytoconstituents which were found to be safe during cytotoxicity analysis. The sedative potential of MEBJ (200 and 400 mg/kg) was determined by employing open field, hole cross, and thiopental sodium-induced sleeping time tests, where a significant reduction of the locomotor performance and an enhancement in the duration of sleeping have been observed, respectively. In addition, mice treated with MEBJ exhibited superior exploration during both elevated plus maze and hole board tests. In parallel, anti-diabetic potency was investigated via alpha-amylase inhibitory assay, where a dose-response increase in the percentage of inhibition has been marked. A similar response, such as an increased percentage of clot lysis, was observed during the thrombolytic test. Furthermore, molecular docking was performed with the identified compounds, demonstrated strong binding affinities to the target receptors of the experiments as mentioned above. Also, ADME/T and toxicological parameters verified the drug-like properties of the identified compounds. Collectively, these results indicate bioactivity of Bischofia javanica, which can be a potential candidate in the food and pharmaceutical industries.

Deciphering the Pharmacological Properties of Methanol Extract of Psychotria calocarpa Leaves by In Vivo, In Vitro and In Silico Approaches.

The present study explores the neuropharmacological, antinociceptive, antidiarrheal, antioxidant, thrombolytic and cytotoxic activity of methanol extract of Psychotria calocarpa leaves (MEPC). In anxiolytic activity testing of MEPC by elevated plus maze test, hole-board test and light-dark test, the extract exhibited a dose-dependent reduction of anxiety while the open field test observed a decreased locomotion. The administration of MEPC revealed a significant dose-dependent reduction of depressant behavior in forced swimming and tail suspension test. Additionally, the antinociceptive and antidiarrheal activity exposed a significant reduction of nociception and diarrheal behavior at the highest dose. In addition, a strong antioxidant activity was observed in DPPH-free radical-scavenging assay (IC50 = 461.05 µg/mL), total phenol content (118.31 ± 1.12 mg) and total flavonoid content (100.85 ± 0.97 mg). The significant clot-lysis activity was also observed with moderate toxicity (LC50 = 247.92 µg/mL) level in the lethality assay of brine shrimp. Moreover, in silico molecular docking study showed that the compound Psychotriasine could offer promising active site interactions for binding proteins. Furthermore, ADME/T and toxicological properties of the compound satisfied the Lipinski's rule of five and Veber rules for drug-like potential and toxicity level. Overall, MEPC had a potential neuropharmacological, antinociceptive, antidiarrheal and antioxidant activity that warranted further investigation.