Immunomodulatory effects of epiphytic Loranthus micranthus leaf extracts collected from two host plants: Psidium guajava and Parkia biglobosa.

BACKGROUND: Immunological abnormalities are implicated in the pathogenesis of many chronic diseases. Due to the drug-related adverse effects of currently available orthodox immunomodulators, natural immunomodulators are being looked upon as potential agents to replace them in therapeutic regimens. This research aimed to investigate the immunomodulatory potential of L. micranthus extracts epiphytic on Psidium guajava (LMPGE) and Parkia biglobosa (LMPBE). METHODS: Phytochemical screening and acute toxicity testing were carried out to identify the phytoconstituents and safety profiles of the extracts. The extracts' innate and adaptive immunomodulatory potentials were determined in experimental animals using in vivo leucocyte mobilization, delayed-type hypersensitivity (DTH) response, hemagglutination antibody titre, and cyclophosphamide-induced myelosuppression models. Levamisole was used as the standard drug throughout the study. RESULTS: Compared to LMPBE, LMPGE contained significantly (p <  0.05) more tannins, cyanogenic glycosides, saponins, reducing sugars, glycosides, flavonoids, and alkaloids. Furthermore, the groups treated with the extracts had a significant (p <  0.05) increase in the total number of leucocytes, neutrophils, basophils, and antibody titers relative to the untreated control. In the same way, the treatment raised TLC in cyclophosphamide-intoxicated rats, with 250 mg/kg b. w. of LMPGE and LMPBE recording 9712.50 ± 178.00 and 8000.00 ± 105.00 ×  109 /L, respectively, compared to 3425.00 ± 2 5.00 × 109 /L in the untreated group. Overall, LMPGE was more effective. CONCLUSIONS: The findings from this study suggest that L. micranthus epiphytic in Psidium guajava and Parkia biglobosa has possible immune stimulating potential.

Changes in nutritional, health benefits, and pharmaceutical potential of raw and roasted tropical almond (Terminalia catappa Linn.) nuts from Nigeria.

Tropical almond (Terminalia catappa Linn.) is highly distributed within the tropics, but appears rather underutilized in developing countries like Nigeria. Specifically, relevant information regards the nutritional, health benefits, and pharmaceutical potential of roasted T. catappa nuts remains scanty. Comparing both raw and roasted T. catappa nuts should provide additional information especially from product development and potential commercial prospect standpoints. The changes in nutritional, health benefits, and pharmaceutical potentials of raw and roasted T. catappa nuts were, therefore, investigated. Whereas the raw T. catappa nuts obtained significantly (p < 0.05) higher protein, ash, moisture, crude fiber, as well as vitamins C, and B1-3 compared to the roasted ones, some contents like carbohydrates, energy, vitamin A, calcium, manganese, zinc, hydrogen cyanide, as well as oxalate would noticeably change (p < 0.05) after the roasting process. Twenty phytochemicals were identified in both raw and roasted samples with the concentrations of quinine, ribalinidine, sapogenin, flavan-3-ol and tannin significantly reduced, while catechin seemed enhanced upon roasting. Promising drug-likeness, pharmacokinetic properties, and safety profiles could be predicted among the phytochemicals. Overall, roasting T. catappa nuts should enhance the nutritional contents, which could aid both absorption and palatability.

Phytochemical Characterization, Functional Nutrition, and Anti-Diabetic Potentials of Leptadenia hastata (pers) Decne Leaves: In Silico and In Vitro Studies.

The geometrical increase in diabetes mellitus (DM) and the undesirable side effects of synthetic drugs have intensified efforts to search for an effective and safe anti-diabetic therapy. This study aimed to identify the antioxidant and anti-diabetic agents in the ethanol extract of Leptadenia hastata (EELH). The phytochemicals, antioxidant vitamins, and minerals present in EELH were determined using standard procedures to achieve this aim. Gas chromatography coupled with mass spectroscopy and flame ionization detector (GC-MS/GC-FID) was employed to identify bioactive compounds. An e-pharmacophore model was generated from the extra precision, and energy-minimized docked position of standard inhibitor, acarbose onto human pancreatic amylase (HPA, PDB-6OCN). It was used to screen the GC-MS/GC-FID library of compounds. The top-scoring compounds were subjected to glide XP-docking and prime MM-GBSA calculation with the Schrodinger suite-v12.4. The Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction of the best-fit compounds was made using SwissADME and PROTOX-II webservers. Further validation of the docking results was performed with the in vitro analysis of the α-amylase and α-glucosidase inhibitory activities. EELH contains appreciable amounts of antioxidant and anti-diabetic phytoconstituents. The top-4 scoring compounds (rutin, epicatechin, kaempferol, and naringenin) from the EELH phytochemical library interacted with amino acid residues within and around the HPA active site. The ADMET prediction shows that epicatechin, kaempferol, and naringenin had favorable drug-likeness, pharmacokinetic properties, and a good safety profile. EELH demonstrated good inhibitory actions against α-amylase and α-glucosidase with 1C50 values of 14.14 and 4.22 µg/mL, respectively. Thus, L hastata phytoconstituents are promising novel candidates for developing an anti-diabetic drug.

A Computational Approach to Elucidate the Interactions of Chemicals From Artemisia annua Targeted Toward SARS-CoV-2 Main Protease Inhibition for COVID-19 Treatment.

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from -7.84 to -7.15 kcal/mol compared with the -6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.

Mechanisms and potential therapeutic targets of hyperinflammatory responses in SARS-CoV-2.

Coronavirus infection is now the leading cause of death globally. Despite the several bedsides- to- bench investigations carried out by researchers all over the world to identify the best prophylactic and therapeutic options for this deadly virus, no novel vaccine or treatment drug has been developed. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with hyper inflammation characterized by excessive release of pro-inflammatory cytokines known as a cytokine storm. The hallmark of this unregulated inflammatory response includes viral sepsis, pneumonitis shock, coagulopathy, and acute respiratory distress syndrome (ARDS) which is the major cause of death in COVID-19 patients. In the midst of cytokine storm and coagulopathy, anti-viral agents alone will not provide the much-needed therapeutic effect. Hence, the need to combine anti-inflammatory agents such as interferons, angiotensinogen converting enzyme 2 (ACE-2) inhibitors, interleukin 6 (IL-6), and Janus kinase (JAK) family inhibitors, anticoagulants and other agents involved in inflammation resolution. This review critically presented a comprehensive overview of SAR-CoV-2, unveiled the mechanisms of the inflammatory response in SARS-CoV-2 and also highlighted possible specific prophylactic and therapeutic interventions that will circumvent inflammatory induced deaths in COVID-19 patients. Keywords: COVID-19; SARS-CoV-2; cytokine storm; coagulopathy and anti-inflammatory.