Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19

Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (Mpro/3CLpro) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources

Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19

The present study aimed to investigate the binding affinity of andrographolide and its derivative i.e., 14-deoxy-11,12-didehydroandrographolide with targets related to COVID-19 and their probable role in regulating multiple pathways in COVID-19 infection. SMILES of both compounds were retrieved from the PubChem database and predicted for probably regulated proteins. The predicted proteins were queried in STRING to evaluate the protein-protein interaction, and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profile of each compound was evaluated using MolSoft and admetSAR 2.0, respectively. Molecular docking was carried using Autodock 4.0. Andrographolide and its derivative were predicted to have a high binding affinity with papain-like protease, coronavirus main proteinase, and spike protein. Molecular dynamics simulation studies were performed for each complex which suggested the strong binding affinities of both compounds with targets. Network pharmacology analysis revealed that both compounds modulated the immune system by regulating chemokine signaling, Rap1 signaling, cytokine-cytokine receptor interaction, MAPK signaling, NF-kappa B signaling, RAS signaling, p53 signaling, HIF-1 signaling, and natural killer cell-mediated cytotoxicity. The study suggests strong interaction of andrographolide and 14-deoxy-11,12-didehydroandrographolide against COVID-19 associated target proteins and exhibited different immunoregulatory pathways. This journal i

Bryophyllum pinnatum leaf extracts prevent formation of renal calculi in lithiatic rats

Background: Bryophyllum pinnatum, commonly known as Pattharcaṭṭa, is used traditionally in ethnomedicinal practices for the treatment of kidney stone and urinary insufficiency. Aim: The present study evaluated the effect of Bryophyllum pinnatum on ethylene glycol (EG)-induced renal calculi in rats. Materials and Methods: Renal calculi were induced in rats by administration of 0.75% EG in drinking water and co-treated orally with standard drug, Cystone (750 mg/kg), or alcoholic and hydro-alcoholic extracts in doses of 100, 200 and 400 mg/kg for 28 days. Weekly body weights were recorded. On day 29, urolithiasis was confirmed by assessing the urinary parameters (urine volume, pH, uric acid, calcium, phosphorus, oxalate, magnesium and creatinine clearance), serum biochemical parameters (creatinine, uric acid, urea, calcium, phosphorus and magnesium), oxidative stress parameters and histology of kidney. Results: Treatment with extracts attenuated the EG-induced decrease in body weight and elevation in urinary parameters (uric acid, calcium, phosphorus and oxalate) and serum biochemical parameters (creatinine, uric acid, urea, calcium, phosphorus and magnesium). Extract treatment also reversed EG-induced decrease in urine volume, pH, magnesium and creatinine clearance, oxidative and histological damages in kidneys. Results were comparable to standard drug, Cystone. Results indicated that EG administration caused renal calculi formation which is prevented by treatment with extracts. The observed antilithiatic effect may be attributed to the presence of high content of phenolics, flavonoids and saponins in the extracts. Conclusion: Bryophyllum pinnatum leaves showed preventive effect against renal calculi formation and validates its ethnomedicinal use in urinary disorders. It further supports its therapeutic potential for the treatment of urinary calculi

Analgesic and anti-inflammatory activity of root bark of Grewia asiatica Linn. in rodents

Background: Grewia asiatica Linn. (Family: Tiliaceae), called Phalsa in Hindi is an Indian medicinal plant used for a variety of therapeutic and nutritional uses. The root bark of the plant is traditionally used in rheumatism (painful chronic inflammatory condition). Aims: The present study demonstrates the analgesic and anti-inflammatory activity of root bark of G. asiatica in rodents. Settings and Design: The methanolic extract of Grewia asiatica (MEGA) and aqueous extract of Grewia asiatica (AEGA) of the bark were prepared and subjected to phytochemical tests and pharmacological screening for analgesic and anti-inflammatory effect in rodents. Materials and Methods: Analgesic effect was studied using acetic acid-induced writhing in mice and hot plate analgesia in rats while anti-inflammatory activity was investigated using carrageenan-induced paw oedema in rats. The MEGA or AEGA was administered orally in doses of 200 and 400 mg/kg/day of body weight. Statistical Analysis: Data were analysed by one-way analysis of variance followed by Dunnett′s test. Results: The extracts showed a significant inhibition of writhing response and increase in hot plate reaction time and also caused a decrease in paw oedema. The effects were comparable with the standard drugs used. Conclusions: The present study indicates that root bark of G. asiatica exhibits peripheral and central analgesic effect and anti-inflammatory activity, which may be attributed to the various phytochemicals present in root bark of G. asiatica

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Context: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders. Objective: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats. Materials and methods: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon. Results: APME or APAE pretreatment significantly (p < .05–.001) prevented AA-induced reduction in body weight and increase in colitis parameters viz. stool consistency, colon weight/length ratio and ulcer score, area and index. Extracts treatment attenuated (p < .001) increase in alkaline phosphatase and lactate dehydrogenase in serum and myeloperoxidase activity and cytokines in colon tissue due to AA administration. Extracts treatment prevented AA-induced elevation in lipid peroxidation and decline in activities of superoxide dismutase and catalase and reduced-glutathione content (p < .05–.001) along with histopathological alterations. PRDS also showed similar ameliorative effect on colitis. Discussion and conclusion: APME and APAE showed a preventive effect on UC, and ameliorated inflammation and oxidative damage in colon. The effects may be attributed to presence of phytochemicals, betulinic acid, β-sitosterol, and glucomannan. In conclusion, the tuber of Amorphophallus paeoniifolius exhibited an anticolitic effect through anti-inflammatory and antioxidant action

Antioxidant and anti-inflammatory activities of Aerva pseudotomentosa leaves

Context: Aerva pseudotomentosa Blatt. & Hallb. (Amaranthaceae), commonly called ‘Bui’, is a medicinal plant of the arid region. It is used for the treatment of inflammatory disorders, such as rheumatic pain, and healing of wounds, which are associated with oxidative stress. Objective: The present study evaluated the antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its anti-inflammatory effect in rats. Material and methods: The aqueous extract (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and hydrogen peroxide free radical scavenging, reducing power, and anti-lipid peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and formalin-induced paw oedema models in rats. APAE (200 and 400 mg/kg) and standard drug, indomethacin (10 mg/kg), were administered orally 1 h before carrageenan/formalin administration and inflammation was noted up to 5 h. Results: HPLC analysis of APAE revealed the presence of rutin. APAE showed significant scavenging effect on DPPH (IC50 49.37 μg/mL) and peroxide (IC50 288.2 μg/mL) radicals. The extract exhibited reducing potential and inhibition of lipid peroxidation. APAE treatment significantly attenuated mean increase in paw volume and exhibited inhibition of paw oedema in both in vivo models with inhibition of 45.11% and 49.42%, respectively at 5 h. Discussion and conclusion: APAE exhibited in vitro antioxidant and anti-inflammatory activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant potential, due to the presence of rutin and other phenolics. This study substantiates folk use of leaves in inflammatory disorders

Antidiabetic activity of Chandraprabha vati – A classical Ayurvedic formulation

Background: Chandraprabha vati is a classical Ayurvedic formulation, markedly used for mitigation of Prameha, which correlates in many ways with obesity, metabolic syndrome and diabetes mellitus. Objective: The present study was aimed to investigate effect of Chandraprabha vati in experimentally-induced hyperglycemia and lipid profile alterations. Materials and methods: Antidiabetic effect of Chandraprabha vati was studied in fifty five Wistar rats. Graded doses of Chandraprabha vati (50, 100 and 200 mg/kg) were administered orally for 7 days to normal and alloxan-hyperglycemic rats (65 mg/kg, intravenously), and to glucose loaded normal rats for oral glucose tolerance test (OGTT). Fasting plasma glucose levels were assessed on different time intervals along with plasma cholesterol and triglycerides. Metformin (500 mg/kg, orally) was used as standard drug. Results: Chandraprabha vati did not cause any significant reduction in plasma glucose levels of normal rats (p > 0.05) but normalized the impaired glucose tolerance at 60 and 120 min (p < 0.05–p < 0.001) in OGTT when compared to vehicle control. In alloxan-hyperglycemic rats, administration of Chandraprabha vati (200 mg/kg) significantly reduced plasma glucose at 3 h, 12 h, 3rd day and 7th day (p < 0.01–p < 0.001) along with reduction in cholesterol and triglycerides levels (p < 0.01–p < 0.001) when compared to diabetic control group. The effects were comparable with metformin. Conclusions: Chandraprabha vati exhibited anti-hyperglycemic effect and attenuated alterations in lipid profile. The results support the use of Chandraprabha vati for correction of Prameha in clinical practice

Oral toxicity of elephant foot yam (Amorphophallus paeoniifolius) tuber in mice

Context: Amorphophallus paeoniifolius tuber is an important constituent of Ayurvedic system of medicine. The tuber of this plant has high medicinal value and is consumed as a food. It is associated with acridity (itchy sensation in mouth and throat) upon oral consumption and presence of high oxalates raphides. Aims: To evaluate the acute and subacute oral toxicity studies of methanolic (APME) and aqueous (APAE) extracts of Amorphophallus paeoniifolius tuber in Swiss albino mice according to OECD guidelines. Methods: In acute oral toxicity study, the mice were orally administered a single dose of APME or APAE (2000 mg/kg) and clinical signs and mortality were observed for 14 days. In subacute (repeated dose) oral toxicity study, the mice were administered once daily, orally with APME or APAE (1000 mg/kg) up to 28 days. The parameters assessed were behavior, clinical signs, body weight, feed and water consumption, urinary, biochemical, hematological and major organ weights and histology. Results: In acute toxicity study, there was no treatment related mortality and morbidity in any of the group. In subacute toxicity study, there were no significant changes in behavior, body weight, feed and water consumption, urinary, biochemical, hematological and organ weight and histological parameters compared to vehicle treated group. There was no treatment related mortality or morbidity. Conclusions: Administration of methanolic and aqueous extracts of Amorphophallus paeoniifolius tuber, individually in acute and 28 days repeated dose in mice, did not exhibit any toxicity or adverse effect at the doses used