In-silico Inhibitory Potential of Triphala Constituents Against Cytochrome P450 2E1 for the Prevention of Thioacetamide-induced Hepatotoxicity

Background: Triphala, which is a combination of fruits of Terminalia chebula, Terminalia bellerica and Embilica officinalis generally recommended as herbal drug formulation in the Indian traditional medicine system. Study Design: To study the in-silico inhibitory potential of Triphala constituents against cytochrome P450 2E1 (CYP2E1) for the prevention of Thioacetamide-induced Hepatotoxicity Place and Duration of Study: The work has been performed at MUP's College of Pharmacy (B Pharm), Degaon, Risod, Washim, Maharashtra, India in between February 2021 to May 2021. Methodology: We have studied the inhibitory potential of Triphala on CYP2E1 by applying molecular docking tools. The major chemical constituents of Triphala i.e. gallic acid, chebulic acid, ellagic acid, epicatechin, syringic acid, and ascorbic acid were docked on CYP2E1. Results: Docking results revealed the very good inhibitory potential of Triphala in terms of binding affinity towards CYP2E1. All the chemical constituents have formed at least 2 and at most 6 hydrogen bonds with the crystal structure of CYP2E1. The binding energies (kcal/mol) of gallic acid, chebulic acid, ellagic acid, epicatechin, syringic acid, and ascorbic acid are -6.1, -7.1, -9.1, -8.3, -6.3, and -5.7, respectively. Ellagic acid has formed strong hydrogen bonds with Thr-303 and Thr-304 with bond length of 1.98 A0 and 2.26 A0 which confirms the excellent inhibition of CYP2E1. Conclusion: These findings can be used to control the CYP2E1-facilitated biotransformation and drug interactions in the development of new chemical entities. In future, these phytoconstituents can be used as lead molecules to overcome the cancer associated with oxidative stress resulting from the hyperactivity of CYP2E1.

Pentagalloylglucose, a phytochemical from Terminalia chebula can efficiently prevent SARS-CoV-2 entry: In Silico study

COVID-19 is the current health challenge across the world. It originated in Wuhan, China, and has now spread to more than 180 countries. It is a zoonotic disease which spreads through droplets. The severity of disease is likely to end with the discovery of vaccines only. Researchers are repurposing drugs to fill the gap between COVID-19 and vaccine designing. Broad-spectrum antiviral drugs are preferred but they exhibit side effects. We have screened pentagalloylglucose present in Terminalia chebula which can prevent SARS-CoV-2 entry to the host cell. In this study, we have taken 8 active phytochemicals of Terminalia chebula which include gallic acid, chebulic acid, chebulanin, neochebulinic acid, ellagic acid, chebulagic acid, chebulinic acid, and pentagalloyglucose against spike proteins (S1 and S2), Replicase Polyprotein, 3C-like protease (3CL pro), Papain-like protease (PLpro), RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. HADDOCK online server, Discovery Studio Visualizer and PyRx Vina tools were used to screen the potential component from T. chebula. It was analysed that pentagalloylglucose can be a better phytochemical against spike protein S1 similar to hemagglutinin of influenza virus. This phytochemical can be further used as a drug against SARS-CoV-2.

High or Low Temperature Extraction, Which Is More Conducive to Triphala Aginst Chronic Pharyngitis?

BackgroundTriphala is a world famous herbal formula, its therapeutic effect on chronic pharyngitis has been confirmed in the majority of patients in China. However, the effects of current industrial extraction methods on its anti chronic pharyngitis components and activities are still unclear Methods:The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. Results:The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocat echin 3 gallate catechin , epicatechin , epicatechin gallate , g allocatechin , quercetin luteolin leucodelphinidin and other flavonoids, phenolic acids such as gallic acid and ellagic acid, alkaloids such as ellipticine , cheilanthifoline, and hydrolyzed tannins such as corilagin and chebulic acid . The high temperature reflux extract and the low temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of 8 active ingredients of gallic acid, ellagic acid, chebulic acid , catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1 to 5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p<0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL 1β (P 0.05), IL 6 (p 0.05), TNF α overexpression ability is stronger than the decompressing inner ebullition extract. Conclusions:gallic acid, ellagic acid, chebulic acid , catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. and high temperature reflux extraction can significantly promote temperature reflux extraction can significantly promote tthe occurrence of the he occurrence of the hydrolysis of tannins significantly increases the content of hydrolysis of tannins significantly increases the content of these components, and the these components, and the antianti--chronic pharyngitis activity is enhanced. chronic pharyngitis activity is enhanced. It is suggested that high temperature It is suggested that high temperature reflux extraction should be used in the treatment of chronic phreflux extraction should be used in the treatment of chronic pharyngitis.aryngitis.

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 μM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of β-cells.